Optically active compound bisoxazoline, method of their preparation and application

FIELD: chemistry.

SUBSTANCE: invention refers to the optically active compounds of bisoxazoline of the formula (1) and the method of their preparation, to the new intermediate products and methods of their preparation, it also refers to cooper asymmetric complex on the basis of the bisoxazoline optically active compound of the formula (1) and the method of preparation of cyclopropalcarbon acids using the asymmetric complex. In the compound of the formula (1) , R1 and R2 are equal and each time stand for C1-6 alkoxy group, C1-6 alkyl group substituted by unsubstituted phenyl group or phenyl group substituted by C1-6 alkyl or C1-6 alkoxy group, R1 and R2 with carbon atom of oxazoline ring, to which they are joined and form cykloalkyl ring which has 3-7 carbon atoms, R3 defines unsubstituted 1-naphthyl group or 2-naphthyl group, or 1-naphthyl group or 2-naphthyl group substituted by at least one C1-6 alkyl group or C1-6 alkoxy group; R4 and R5 are equal and each of them stands for hydrogen atom or C1-6 alkyl group or R4 and R5 with carbon atom, to which they are joined, form cykloalkyl ring which has 3-6 carbon atom and * mean asymmetrical center.

EFFECT: usage of the asymmetrical complex allows getting cyclopropanecarboxylic acid in high yields.

16 cl, 11 ex

 

The technical field

This invention relates to optically active compounds of bisoxazoline, methods for their preparation and their use.

The level of technology

Known methods for producing optically active cyclopropane compounds, which are very important as intermediate compounds in the synthesis of agricultural chemicals, such as synthetic insecticides PYRETHROID type, pharmaceuticals, etc. and an illustrative example of which is the (+)-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarbonyl acid, properally olefins by asymmetric reactions using optically active compounds bisoxazoline as a ligand (for example, JP 11-171874 A, Tetrahedron Lett.,32, 7373 (1991)). These methods are relatively good on diastereoselectivity (TRANS-isomer/CIS-isomer) and enantioselectivity. However, from a manufacturing standpoint, it is desirable to further improve the yield of the desired optically active compounds of cyclopropane.

The invention

According to this invention, optically active compound bisoxazoline with afterglow as a catalytic component, asymmetric synthesis, can be easily obtained, as well as optically active compound can be obtained with high yield for the no beneficial use of industrial asymmetric catalyst, containing optically active compound bisoxazoline and the connection of copper.

That is, the present invention relates to optically active compound of bisoxazoline represented by the formula (1):

where R1and R2are the same and each means C1-6accelgroup, substituted or unsubstituted arakalgudu or substituted or unsubstituted panelgroup or R1and R2together with the carbon atom ring oxazoline to which they are attached, form a ring; R3means substituted or unsubstituted afterglow (preferably 1-afterglow or 2-aftercrop); R4and R5are the same and each means a hydrogen atom or a C1-6accelgroup, or R4and R5together with the carbon atom to which they are attached, form a ring cycloalkyl having 3-6 carbon atoms; and * indicates an asymmetric center; the method of its production and its use.

The best option is the implementation of the present invention

First, the disclosed optically active compound bisoxazoline represented by the formula (1) (hereafter referred to simply as optically active compound bisoxazoline (1)), which is a new connection.

Examples of C1-6altergroup represented by R1and R2include al is rgruppe straight or branched chain, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl and n-hexyl, and, as examples of the ring formed by linking R1and R2together with the carbon atom ring oxazoline to which they are attached, can be cast ring cycloalkyl having 3-7 carbon atoms. Examples of ring cycloalkyl include a cyclopropane ring, ring CYCLOBUTANE, ring cyclopentane, the cyclohexane ring and the ring Cycloheptane.

Examples of substituted or unsubstituted of panelgroup represented by R1and R2include the unsubstituted panelgroup; panelgroup, substituted C1-6the alkyl, such as 3-and 4 were-methylphenidate, and panelgroup, substituted C1-6alkoxygroup (for example, methoxy, ethoxy, propoxy, butoxy, pentyloxy and hexyloxy), such as 2-methoxyphenyl, 3-methoxyphenyl and 4-methoxyphenyl.

Substituted or unsubstituted arlbergpass is, for example, C1-6accelgroup, replaced the above substituted or unsubstituted allgroups. The examples include benzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 1-naphthylmethyl and 2-naphthylmethyl.

In the formula representing the optically active compound bisoxazoline (1), substituted or unsubstituted afterrepair represented by R3 in addition to the unsubstituted 1-naphthyl or 2-aftercrop is, for example, 1-naphthyl or 2-aftercrop, substituted with at least one C1-6the alkyl or C1-6alkoxygroup. Examples of C1-6the alkyl or C1-6alkoxygroup include those given as examples of the substituent R1or R2. Specifically, it is, for example, 4-fluoro-1-naphthyl, 2-methyl-1-naphthyl, 4-methyl-1-naphthyl, 2-methoxy-1-naphthyl, 2-ethoxy-1-naphthyl, 4-methoxy-1-naphthyl, 2,4-dimethoxy-1-naphthyl, 2-naphthyl, 7-methyl-2-naphthyl, 1-n-propyl-2-naphthyl, 6-methoxy-2-naphthyl and 3,8-dimethoxy-2-aftercrop. Including 1-naphthyl and 2-aftercrop preferred.

Examples of C1-6altergroup represented by R4and R5include C1-3accelgroup, such as methyl, ethyl, n-propyl and isopropylate and butyl, pentyl and exirgruppen. Examples of the ring formed by linking R4and R5together with the carbon atom ring oxazoline to which they are attached, can be ring cycloalkyl having 3-6 carbon atoms. Examples of ring cycloalkyl include a cyclopropane ring, ring CYCLOBUTANE, ring cyclopentane and the cyclohexane ring. Preferably, R4and R5means a hydrogen atom, a C1-3altergroup or ring cycloalkyl having 3-6 carbon atoms, formed by the binding of R4and R5together with the atom angle of the ode ring oxazoline, to which they are attached, and, more preferably, they mean C1-3altergroup.

In the compounds of bisoxazoline represented by the formula (1), there are two asymmetric carbon atom marked with *, and compounds in which both asymmetric carbon atoms are in (S) or (R) configurations, are preferred.

Specific examples of such optically active compounds of bisoxazoline (1) include bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-Dietrichstein]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di-n-propiconazole]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di-n-butylanisole]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-diisobutylamine]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di-n-partylocation]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di-n-sexylactation]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-dibenzalacetone]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methylbenzyl)oxazoline]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methylbenzyl)oxazoline]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methylbenzyl)oxazoline]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxybenzyl)oxazoline]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methoxybenzyl)oxazoline]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxybenzyl)oxazoline]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(1-naphthylmethyl)oxazoline]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(2-naphthylmethyl)oxazoline]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-diphenyloxazole]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(3-were)ACS is Zolin]]methane,

bis[2-[(4S)-(1-naphthyl)-5,5-di(4-were)oxazoline]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxyphenyl)oxazoline]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methoxyphenyl)oxazoline]]methane, bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxyphenyl)oxazoline]]methane, bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopropane]]]methane, bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-CYCLOBUTANE]]]methane, bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopentane]]]methane, bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclohexane]]]methane, bis[2-[Spiro[(4S)-methoxazole-5,1'-Cycloheptane]]]methane,

2,2-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-Dietrichstein]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-propiconazole]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-butylanisole]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-diisobutylamine]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-partylocation]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-sexylactation]]propane, 2,2-[2-bis[2-(4S)-(1-naphthyl)-5,5-dibenzalacetone]]propane, 2,2-[2-bis[2-bis(4S)-(1-naphthyl)-5,5-di(2-methylbenzyl)oxazoline]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methylbenzyl)oxazoline]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methylbenzyl)oxazoline]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxybenzyl)oxazoline]]propane, 2,2-bis[(4S)-(1-naphthyl)-5,5-di(3-methoxybenzyl)oxazoline]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxybenzyl)oxazoline]]propane,

2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di(1-naphthylmethyl)oxazoline]]disappear to the, 2,2-bis[(4S)-(1-naphthyl)-5,5-di(2-naphthylmethyl)oxazoline]]propane, 2,2-bis[(4S)-(1-naphthyl)-5,5-diphenyloxazole]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-were)oxazoline]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-were)oxazoline]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxyphenyl)oxazoline]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methoxyphenyl)oxazoline]]propane, 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxyphenyl)oxazoline]]propane, 2,2-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopropane]]]propane, 2,2-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-CYCLOBUTANE]]]propane, 2,2-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopentane]]]propane, 2,2-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclohexane]]]propane, 2,2-bis[2-[Spiro[(4S)-methoxazole-5,1'-Cycloheptane]]]propane,

3,3-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-Dietrichstein]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-propyl-2-oxazoline]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-butylanisole]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-diisobutylamine]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-partylocation]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-sexylactation]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-dibenzalacetone]]pentane, 3,3-bis[2-bis[(4S)-(1-naphthyl)-5,5-di(2-methylbenzyl)oxazoline]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methylbenzyl)oxazoline]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methylbenzyl)oxazoline]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxybenzyl)oxazoline]]is Intan, 3,3-bis[(4S)-(1-naphthyl)-5,5-di(3-methoxybenzyl)oxazoline]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxybenzyl)oxazoline]]pentane,

3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di(1-naphthylmethyl)oxazoline]]pentane, 3,3-[2-bis[(4S)-(1-naphthyl)-5,5-di(2-naphthylmethyl)oxazoline]]pentane, 3,3-[2-bis[(4S)-(1-naphthyl)-5,5-diphenyloxazole]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-were)oxazoline]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-were)oxazoline]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxyphenyl)oxazoline]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methoxyphenyl)oxazoline]]pentane, 3,3-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxyphenyl)oxazoline]]pentane, 3,3-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopropane]]]pentane, 3,3-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-CYCLOBUTANE]]]pentane, 3,3-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopentane]]]pentane, 3,3-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclohexane]]]pentane, 3,3-bis[2-[Spiro[(4S)-methoxazole-5,1'-Cycloheptane]]]pentane,

4,4-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-diethyl-2-oxazoline]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-propiconazole]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-butylanisole]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-diisobutylamine]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-partylocation]]heptane, 4,4-[2-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-sexylactation]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-dibenzalacetone]]heptane, 4,4-bis[2-bis[(4S)-(1-naphthyl)-5,5-di(2-methylbenzyl)on casalin]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methylbenzyl)oxazoline]]heptane, 4,4-[2-[(4S)-(1-naphthyl)-5,5-di(4-methylbenzyl)oxazoline]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxybenzyl)oxazoline]]heptane, 4,4-[2-bis[(4S)-(1-naphthyl)-5,5-di(3-methoxybenzyl)oxazoline]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxybenzyl)oxazoline]]heptane,

4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di(1-naphthylmethyl)oxazoline]]heptane, 4,4-[2-bis[(4S)-(1-naphthyl)-5,5-di(2-naphthylmethyl)oxazoline]]heptane, 4,4-bis[(4S)-(1-naphthyl)-5,5-diphenyloxazole]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-were)oxazoline]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-were)oxazoline]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxyphenyl)oxazoline]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methoxyphenyl)oxazoline]]heptane, 4,4-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxyphenyl)oxazoline]]heptane, 4,4-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopropane]]]heptane, 4,4-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-CYCLOBUTANE]]]heptane, 4,4-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopentane]]]heptane, 4,4-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclohexane]]]heptane, 4,4-bis[2-[Spiro[(4S)-methoxazole-5,1'-Cycloheptane]]]heptane,

1,1-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-Dietrichstein]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-propyl-2-oxazoline]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-butylanisole]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-diisobutylamine]]cyclopropane,1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-partylocation]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-sexylactation]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-dibenzalacetone]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methylbenzyl)oxazoline]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methylbenzyl)oxazoline]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methylbenzyl)oxazoline]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxybenzyl)oxazoline]]cyclopropane, 1,1-bis[(4S)-(1-naphthyl)-5,5-di(3-methoxybenzyl)oxazoline]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxybenzyl)oxazoline]]cyclopropane,

1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(1-naphthylmethyl)oxazoline]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-naphthylmethyl)oxazoline]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-diphenyloxazole]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-were)oxazoline]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-were)oxazoline]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxyphenyl)oxazoline]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methoxyphenyl)oxazoline]]cyclopropane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxyphenyl)oxazoline]]cyclopropane, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopropane]]]cyclopropane, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopentane]]]cyclopropane, 1,1-bis[2-[Spiro[(4S)-methoxazole-5,1'-Cycloheptane]]]cyclopropane,

1,1-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-Dietrichstein]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-ropyl-2-oxazoline]]CYCLOBUTANE, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-butylanisole]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-diisobutylamine]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-partylocation]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-sexylactation]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-dibenzalacetone]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methylbenzyl)oxazoline]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methylbenzyl)oxazoline]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methylbenzyl)oxazoline]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxybenzyl)oxazoline]]cyclobutyl, 1,1-bis[(4S)-(1-naphthyl)-5,5-di(3-methoxybenzyl)oxazoline]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxybenzyl)oxazoline]]CYCLOBUTANE,

1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(1-naphthylmethyl)oxazoline]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-naphthylmethyl)oxazoline]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-diphenyloxazole]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-were)oxazoline]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-were)oxazoline]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxyphenyl)oxazoline]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methoxyphenyl)oxazoline]]cyclobutyl, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxyphenyl)oxazoline]]cyclobutyl, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopropane]]]cyclobutyl, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-CYCLOBUTANE]]]cyclobutyl, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopentane]]CYCLOBUTANE, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclohexane]]]cyclobutyl, 1,1-bis[2-[Spiro[(4S)-methoxazole-5,1'-Cycloheptane]]]CYCLOBUTANE,

1,1-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-Dietrichstein]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-propiconazole]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-butylanisole]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-diisobutylamine]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-partylocation]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-sexylactation]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-dibenzalacetone]]cyclopentane, 1,1-bis[2-bis[(4S)-(1-naphthyl)-5,5-di(2-methylbenzyl)oxazoline]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methylbenzyl)oxazoline]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methylbenzyl)oxazoline]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxybenzyl)oxazoline]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methoxybenzyl)oxazoline]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxybenzyl)oxazoline]]cyclopentane,

1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(1-naphthylmethyl)oxazoline]]cyclopentane, 1,1-bis[(4S)-(1-naphthyl)-5,5-di(2-naphthylmethyl)oxazoline]]cyclopentane, 1,1-bis[(4S)-(1-naphthyl)-5,5-diphenyloxazole]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-were)oxazoline]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-were)oxazoline]]pentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxyphenyl)oxazoline]]cyclopen the Academy of Sciences, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methoxyphenyl)oxazoline]]cyclopentane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxyphenyl)oxazoline]]cyclopentane, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopropane]]]cyclopentane, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-CYCLOBUTANE]]]cyclopentane, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopentane]]]cyclopentane, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclohexane]]]cyclopentane, 1,1-bis[2-[Spiro[(4S)-methoxazole-5,1'-Cycloheptane]]]cyclopentane,

1,1-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-Dietrichstein]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-propiconazole]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-butylanisole]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-diisobutylamine]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-partylocation]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di-n-sexylactation]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-dibenzalacetone]]cyclohexane, 1,1-bis[2-bis[(4S)-(1-naphthyl)-5,5-di(2-methylbenzyl)oxazoline]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methylbenzyl)oxazoline]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methylbenzyl)oxazoline]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxybenzyl)oxazoline]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methoxybenzyl)oxazoline]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxybenzyl)oxazoline]]cyclohexane,

1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(1-on teletel)oxazoline]]cyclohexane, 1,1-bis[(4S)-(1-naphthyl)-5,5-di(2-naphthylmethyl)oxazoline]]cyclohexane, 1,1-bis[(4S)-(1-naphthyl)-5,5-diphenyloxazole]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-were)oxazoline]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-were)oxazoline]]hexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(2-methoxyphenyl)oxazoline]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(3-methoxyphenyl)oxazoline]]cyclohexane, 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-di(4-methoxyphenyl)oxazoline]]cyclohexane, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopropane]]]cyclohexane, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-CYCLOBUTANE]]]cyclohexane, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclopentane]]]cyclohexane, 1,1-bis[2-[Spiro[(4S)-(1-naphthyl)oxazoline-5,1'-cyclohexane]]]cyclohexane, 1,1-bis[2-[Spiro[(4S)-methoxazole-5,1'-Cycloheptane]]]cyclohexane and such compounds in which 1-aftercrop in the fourth position of the substituted 2-aftercrop, such as bis[2-[(4S)-(2-naphthyl)-5,5-dimethyloxazole]]methane; such compounds in which the configuration (4S) at the fourth position is replaced by (4R), such as bis[2-[(4R)-(1-naphthyl)-5,5-dimethyloxazole]]methane and bis[2-[(4R)-(2-naphthyl)-5,5-dimethyloxazole]]methane.

Optically active compounds of bisoxazoline (1) can be obtained by the interaction of the optically active dumenigo compounds represented by formula (2):

where R1, R2, R3, R4R 5and * have the above values, which is a new connection (hereafter referred to as optically active diamine connection (2)) with a Lewis acid.

Examples of optically active diamedix compounds (2) include N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-ethylbutyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-propylpentyl]propane 1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-butylphenyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-isobutyl-4-methylpentyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-intergates]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-hexyloxy]propane-1,3-diamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-benzyl-3-phenylpropyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methylbenzyl)-3-(2-were)propyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methylbenzyl)-3-(3-were)propyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methylbenzyl)-3-(4-were)propyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methoxybenzyl)-3-(2-methoxyphenyl)propyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methoxybenzyl)-3-(3-methoxyphenyl)propyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methoxybenzyl)-3-(4-methoxyphenyl)propyl]propane-1,3-diamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(1-naphthylmethyl)-3-(1-NAF shall yl)propyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-naphthylmethyl)-3-(2-naphthyl)propyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-diphenylether]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-were)ethyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(4-were)ethyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(2-methoxyphenyl)ethyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-methoxyphenyl)ethyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxyisopropyl)methyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]propane-1,3-diamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-ethylbutyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-propylpentyl]-2,2-DIMETHYLPROPANE-1,3-diamide N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-butylphenyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-isobutyl-4-methylpentyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-intergates]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-hexyloxy]-2,2-DIMETHYLPROPANE-1,3-diamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-benzyl-3-phenylpropyl]-2,2-dimethy is propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methylbenzyl)-3-(2-were)propyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methylbenzyl)-3-(3-were)propyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methylbenzyl)-3-(4-were)propyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methoxybenzyl)-3-(2-methoxyphenyl)propyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methoxybenzyl)-3-(3-methoxyphenyl)propyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methoxybenzyl)-3-(4-methoxyphenyl)propyl]-2,2-DIMETHYLPROPANE-1,3-diamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(1-naphthylmethyl)-3-(1-naphthyl)propyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-naphthylmethyl)-3-(2-naphthyl)propyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-diphenylether]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-were)ethyl)-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(4-were)ethyl)-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(2-methoxyphenyl)ethyl)-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-methoxyphenyl)ethyl)-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxyisopropyl)methyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl(1-hydroxycyclopent)methyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]-2,2-DIMETHYLPROPANE-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]-2,2-DIMETHYLPROPANE-1,3-diamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-ethylbutyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-propylpentyl]-2,2-diethylpropane-1,3-diamide N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-butylphenyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-isobutyl-4-methylpentyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-intergates]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-hexyloxy]-2,2-diethylpropane-1,3-diamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-benzyl-3-phenylpropyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methylbenzyl)-3-(2-were)propyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methylbenzyl)-3-(3-were)propyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methylbenzyl)-3-(4-were)propyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methoxybenzyl)-3-(2-methoxyphenyl)propyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methoxybenzyl)-3-(3-methoxyphenyl)propyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methoxybenzyl)-3-(4-methoxyphenyl)propyl]-2,2-diethylpropane-1,3-diamide,

N,N'-bis[1S)-(1-naphthyl)-2-hydroxy-2-(1-naphthylmethyl)-3-(1-naphthyl)propyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-naphthylmethyl)-3-(2-naphthyl)propyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-diphenylether]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-were)ethyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(4-were)ethyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(2-methoxyphenyl)ethyl]-2,2-diethylpropane-1,3-diamide, N,N'bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-methoxyphenyl)ethyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxyisopropyl)methyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]-2,2-diethylpropane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]-2,2-diethylpropane-1,3-diamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-ethylbutyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-propylpentyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-butylphenyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-isobutyl-4-methylpentyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-intergates]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-hexyloxy]-2,2-di(n-propyl)propane-1,3-diamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-benzyl-3-phenylpropyl]-2,2-di(n-propyl)propane-1,3-di the Ministry of foreign Affairs, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methylbenzyl)-3-(2-were)propyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methylbenzyl)-3-(3-were)propyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methylbenzyl)-3-(4-were)propyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methoxybenzyl)-3-(2-methoxyphenyl)propyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methoxybenzyl)-3-(3-methoxyphenyl)propyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methoxybenzyl)-3-(4-methoxyphenyl)propyl]-2,2-di(n-propyl)propane-1,3-diamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(1-naphthylmethyl)-3-(1-naphthyl)propyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-naphthylmethyl)-3-(2-naphthyl)propyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-diphenylether]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-were)ethyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(4-were)ethyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(2-methoxyphenyl)ethyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2 di(3-methoxyphenyl)ethyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxyisopropyl)methyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent the l)methyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]-2,2-di(n-propyl)propane-1,3-diamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]-2,2-di(n-propyl)propane-1,3-diamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-ethylbutyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-propylpentyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-butylphenyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-isobutyl-4-methylpentyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-intergates]cyclopropane-1,1-dicarboxamide, N,N'bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-hexyloxy]cyclopropane-1,1-dicarboxamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-benzyl-3-phenylpropyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methylbenzyl)-3-(2-were)propyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methylbenzyl)-3-(3-were)propyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methylbenzyl)-3-(4-were)propyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methoxybenzyl)-3-(2-methoxyphenyl)propyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methoxybenzyl)-3-(3-methoxyphenyl)propyl]qi is looprope-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methoxybenzyl)-3-(4-methoxyphenyl)propyl]cyclopropane-1,1-dicarboxamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(1-naphthylmethyl)-3-(1-naphthyl)propyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-naphthylmethyl)-3-(2-naphthyl)propyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-diphenylether]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-were)ethyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(4-were)ethyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(2-methoxyphenyl)ethyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-methoxyphenyl)ethyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxyisopropyl)methyl]cyclopropane-1,1-dicarboxamide, N,N'bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]cyclopropane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]cyclopropane-1,1-dicarboxamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-ethylbutyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-propylpentyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthas is l)-2-hydroxy-2-n-butylphenyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-isobutyl-4-methylpentyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-intergates]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-hexyloxy]CYCLOBUTANE-1,1-dicarboxamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-benzyl-3-phenylpropyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methylbenzyl)-3-(2-were)propyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methylbenzyl)-3-(3-were)propyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methylbenzyl)-3-(4-were)propyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methoxybenzyl)-3-(2-methoxyphenyl)propyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methoxybenzyl)-3-(3-methoxyphenyl)propyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methoxybenzyl)-3-(4-methoxyphenyl)propyl]CYCLOBUTANE-1,1-dicarboxamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(1-naphthylmethyl)-3-(1-naphthyl)propyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-naphthylmethyl)-3-(2-naphthyl)propyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-diphenylether]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-were)ethyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(4-were)ethyl]CYCLOBUTANE-1,1-dicarboxy the Ministry of foreign Affairs, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(2-methoxyphenyl)ethyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-methoxyphenyl)ethyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxyisopropyl)methyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]CYCLOBUTANE-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]CYCLOBUTANE-1,1-dicarboxamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-ethylbutyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-propylpentyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-butylphenyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-isobutyl-4-methylpentyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-intergates]cyclopentane-1,1-dicarboxamide, N,N'bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-hexyloxy]cyclopentane-1,1-dicarboxamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-benzyl-3-phenylpropyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methylbenzyl)-3-(2-were)propyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methylbenzyl)-3-(3-methylphen the l)propyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methylbenzyl)-3-(4-were)propyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methoxybenzyl)-3-(2-methoxyphenyl)propyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methoxybenzyl)-3-(3-methoxyphenyl)propyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methoxybenzyl)-3-(4-methoxyphenyl)propyl]cyclopentane-1,1-dicarboxamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(1-naphthylmethyl)-3-(1-naphthyl)propyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-naphthylmethyl)-3-(2-naphthyl)propyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-diphenylether]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-were)ethyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(4-were)ethyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(2-methoxyphenyl)ethyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-methoxyphenyl)ethyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxyisopropyl)methyl]cyclopentane-1,1-dicarboxamide, N,N'bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]cyclopentane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-NAF is Il)(1-hydroxycyclohexyl)methyl]cyclopentane-1,1-dicarboxamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-ethylbutyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-propylpentyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-butylphenyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-isobutyl-4-methylpentyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-intergates]cyclohexane-1,1-dicarboxamide, N,N'bis[(1S)-(1-naphthyl)-2-hydroxy-2-n-hexyloxy]cyclohexane-1,1-dicarboxamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-benzyl-3-phenylpropyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methylbenzyl)-3-(2-were)propyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methylbenzyl)-3-(3-were)propyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methylbenzyl)-3-(4-were)propyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(2-methoxybenzyl)-3-(2-methoxyphenyl)propyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(3-methoxybenzyl)-3-(3-methoxyphenyl)propyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(4-methoxybenzyl)-3-(4-methoxyphenyl)propyl]cyclohexane-1,1-dicarboxamide,

N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-(1-naphthylmethyl)-3-(1-naphthyl)propyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-who aftil)-2-hydroxy-2-(2-naphthylmethyl)-3-(2-naphthyl)propyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-diphenylether]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-were)ethyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(4-were)ethyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(2-methoxyphenyl)ethyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2,2-di(3-methoxyphenyl)ethyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxyisopropyl)methyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclopent)methyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]cyclohexane-1,1-dicarboxamide, N,N'-bis[(1S)-(1-naphthyl)(1-hydroxycyclohexyl)methyl]cyclohexane-1,1-dicarboxamide; and such compounds in which 1-aftercrop in position 1 group linked to the nitrogen atom of amide, substituted 2-afterrepair; and such compounds in which the configuration (1S) replaced by (1R).

As the Lewis acid is usually used aprotic acids, and their examples include tetraethoxy titanium, such as tetraisopropoxide titanium; titanium halides such as titanium chloride; tetraethoxide aluminum, such as tetraisopropoxide aluminum; aluminum halides such as aluminum chloride, dichloride ethylaluminum and chloride is ethylaluminum; trialkylaluminium, such as trimethylaluminum and triethylaluminum; tin halides, such as dichloride dimethylurea and tin chloride; zinc halides such as zinc chloride; alkoxyl, such as diisopropoxide; halides of zirconium such as zirconium chloride; and hafnium halides, such as hafnium chloride. Such Lewis acid can be used individually, or two or more of them may be used in the form of a mixture. The amount of Lewis acid, which must be used, usually from about 0.001 to 5 mol, preferably from about 0.01 to 1 mol relative to 1 mol of the optically active dumenigo connection (2).

Optically active compound bisoxazoline (1) can be obtained by the interaction of the optically active dumenigo connection (2) with a Lewis acid, and usually this process can be carried out in the presence of a solvent. Type of solvent is not limited in a special way if it is an inert solvent in the reaction, and examples include aromatic hydrocarbon solvents such as toluene and xylene; aliphatic hydrocarbon solvents such as heptane and octane; halogenated hydrocarbon solvents such as chlorobenzene, dichloromethane and dichloroethane. They can be used alone or as a mixture. The amount of solvent that the debtor is about to be used, not specifically limited, and usually it is from about 2 to 200 parts by mass relative to 1 part by weight of optically active dumenigo connection (2).

The reaction temperature for the interaction of the Lewis acid typically ranges from about 50 to 250°C, preferably from about 60 to 180°C. the reaction Time is not specifically limited, and the reaction can be stopped when they find that the optically active diamine connection (2) disappears, or when they find that the reaction slows down, analyzing the course of the reaction by conventional means such as gas chromatography, high performance liquid chromatography and the like.

After completion of the reaction the reaction mixture is concentrated to obtain optically active compound bisoxazoline (1). Although optically active compound bisoxazoline (1), thus obtained, can be used as such to obtain an asymmetric complex of copper, as described hereafter, preferably, it is used after purification by conventional means of purification, such as column chromatography, recrystallization and the like. In addition, optically active compound bisoxazoline (1) can be isolated by mixing the reaction mixture with an aqueous alkaline solution such as an aqueous solution of the bicarbonate is sodium and after removing insoluble substances by filtration, if necessary, the carrying out of processing by extracting and concentrating the resulting organic layer.

Optically active diamine compound (2) can be obtained by the interaction of the optically active amerosport represented by the formula (3):

where R1, R2, R3and * have the above values (hereafter referred to as optically active amerosport (3)), with the compound of malonic acid represented by the formula (4):

where R4and R5have the above meanings and Z means alkoxygroup or halogen atom (hereafter referred to simply as the compound of malonic acid (4)).

Examples of optically active amerosport (3) include (R)-1-amino-1-(1-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(1-naphthyl)-2-ethyl-2-butanol, (R)-1-amino-1-(1-naphthyl)-2-n-propyl-2-pentanol, (R)-1-amino-1-(1-naphthyl)-2-n-butyl-2-hexanol, (R)-1-amino-1-(1-naphthyl)-2-isobutyl-4-methyl-2-pentanol, (R)-1-amino-1-(1-naphthyl)-2-n-pentyl-2-heptanol, (R)-1-amino-1-(1-naphthyl)-2-n-hexyl-2-octanol, (R)-1-amino-1-(1-naphthyl)-2-benzyl-3-phenyl-2-propanol, (R)-1-amino-1-(1-naphthyl)-2-(3-methylbenzyl)-3-(3-were)-2-propanol, (R)-1-amino-1-(1-naphthyl)-2-(2-methylbenzyl)-3-(2-were)-2-propanol, (R)-1-amino-1-(1-naphthyl)-2-(4-methylbenzyl)-3-(4-were)-2-propanol, (R)-1-amino-1-(1-naphthyl)-2-(2-methoxybenzyl)-3-(2-m is toxigenic)-2-propanol, (R)-1-amino-1-(1-naphthyl)-2-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-propanol, (R)-1-amino-1-(1-naphthyl)-2-(4-methoxybenzyl)-3-(4-methoxyphenyl)-2-propanol,

(R)-1-amino-1-(1-naphthyl)-2-(1-naphthylmethyl)-3-(1-naphthyl)-2-propanol, (R)-1-amino-1-(1-naphthyl)-2-(2-naphthylmethyl)-3-(2-naphthyl)-2-propanol, (R)-2-amino-2-(1-naphthyl)-1,1-diphenylethanol, (R)-2-amino-2-(1-naphthyl)-1,1-di(3-were)ethanol, (R)-2-amino-2-(1-naphthyl)-1,1-di(4-were)ethanol, (R)-2-amino-2-(1-naphthyl)-1,1-di(2-methoxyphenyl)ethanol, (R)-2-amino-2-(1-naphthyl)-1,1-di(3-methoxyphenyl)ethanol, (R)-2-amino-2-(1-naphthyl)-1,1-di(4-methoxyphenyl)ethanol, 1-[(R)-amino-(1-naphthyl)methyl]cyclopropane, 1-[(R)-amino-(1-naphthyl)methyl]cyclobutanol, 1-[(R)-amino-(1-naphthyl)methyl]Cyclopentanol, 1-[(R)-amino-(1-naphthyl)methyl]cyclohexanol, 1-[(R)-amino-(1-naphthyl)methyl]cycloheptanol,

(R)-1-amino-1-(2-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(2-naphthyl)-2-ethyl-2-butanol, (R)-1-amino-1-(2-naphthyl)-2-n-propyl-2-pentanol, (R)-1-amino-1-(2-naphthyl)-2-n-butyl-2-hexanol, (R)-1-amino-1-(2-naphthyl)-2-isobutyl-4-methyl-2-pentanol, (R)-1-amino-1-(2-naphthyl)-2-n-pentyl-2-heptanol, (R)-1-amino-1-(2-naphthyl)-2-n-hexyl-2-octanol, (R)-1-amino-1-(2-naphthyl)-2-benzyl-3-phenyl-2-propanol, (R)-1-amino-1-(2-naphthyl)-2-(3-methylbenzyl)-3-(3-were)-2-propanol, (R)-1-amino-1-(2-naphthyl)-2-(2-methylbenzyl)-3-(2-were)-2-propanol, (R)-1-amino-1-(2-naphthyl)-2-(4-methylbenzyl)-3-(4-were)-2-propanol, (R)-1-amino-1-(2-naphthyl)-2-(2-methoxybenzyl)-3-(2-methoxyphenyl)-2-propanol, (R)-1-amino-1-(2-NAF shall yl)-2-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-propanol, (R)-1-amino-1-(2-naphthyl)-2-(4-methoxybenzyl)-3-(4-methoxyphenyl)-2-propanol,

(R)-1-amino-1-(2-naphthyl)-2-(1-naphthylmethyl)-3-(1-naphthyl)-2-propanol, (R)-1-amino-1-(2-naphthyl)-2-(2-naphthylmethyl)-3-(2-naphthyl)-2-propanol, (R)-2-amino-2-(2-naphthyl)-1,1-diphenylethanol, (R)-2-amino-2-(2-naphthyl)-1,1-di(3-were)ethanol, (R)-2-amino-2-(2-naphthyl)-1,1-di(4-were)ethanol, (R)-2-amino-2-(2-naphthyl)-1,1-di(2-methoxyphenyl)ethanol, (R)-2-amino-2-(2-naphthyl)-1,1-di(3-methoxyphenyl)ethanol, (R)-2-amino-2-(2-naphthyl)-1,1-di(4-methoxyphenyl)ethanol, 1-[(R)-amino-(2-naphthyl)methyl]cyclopropane, 1-[(R)-amino-(2-naphthyl)methyl]cyclobutanol, 1-[(R)-amino-(2-naphthyl)methyl]Cyclopentanol, 1-[(R)-amino-(2-naphthyl)methyl]cyclohexanol, 1-[(R)-amino-(2-naphthyl)methyl]cycloheptanol and such compounds, where the configuration (R) replaced by (S). Such optically active amerosport (3) may be in the form of additive salts with an acid, such as hydrochloride, sulfate and acetate.

Optically active amerosport (3) can be obtained by the optical separation of the compounds amerosport, as described hereafter, or the interaction of the optically active complex ester of the amino acids with the corresponding Grignard reagent. Optically active ester of the amino acids can be obtained by etherification of optically active amino acids, which can be obtained by the method described in Tetrahedron 55(1999)11295-11308, in a known manner or way, opican the m here next. In addition, if necessary, the amino group of the optically active complex ester of the amino acids may be protected by a suitable protecting group, and after interaction with a Grignard reagent, the protective group can be removed.

In the formula of the compound of malonic acid (4) Z means alkoxygroup or halogen atom. Examples of alkoxy include alkoxygroup having 1-6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, pentyloxy and hexyloxy. Examples of the halogen atom include a chlorine atom and bromine.

Examples of compounds of malonic acid (4) involve complex diesters of malonic acid, such as diethylmalonate, diethylmalonate, dimethyldodecylamine, dimethylgermylene, dimethyldi(n-propyl)malonate, dimethyl-1,1-cyclopropanedicarboxylic, dimethyl-1,1-cyclobutanedicarboxylate, dimethyl-1,1-cyclopentanecarboxylate and dimethyl-1,1-cyclohexanedicarboxylic; and halides of malonic acid, such as malonic acid dichloride, the dichloride dimethylmaleic acid dichloride diethylmalonate acid dichloride, di(n-propyl)malonic acid dichloride 1,1-dichloropropanone acid dichloride 1,1-cyclobutanedicarboxylic acid dichloride 1,1-cyclopentanecarbonyl acid dichloride 1,1-cyclohexanedicarboxylic acid and malonic acid dibromide.

The number of compounds is of malonic acid (4), which should be used, usually from about 0.3 to 2 mol, preferably from about 0.5 to 1 mol relative to 1 mol of the optically active amerosport (3).

The interaction of optically active amerosport (3) with a compound of malonic acid (4) is usually carried out by mixing and bringing them into contact with each other in the presence of a solvent. The solvent, which should be used is not specifically limited if it is inert solvent in the reaction, and examples include the same solvents as those listed as examples above regarding the interaction of optically active dumenigo compounds (2) and Lewis acid.

The reaction temperature in the case of applying a complex diapir malonic acid, in which Z means alkoxygroup, as a compound of malonic acid (4), is usually from about 50 to 250°C, preferably about 60 to 180°C. In this case, the reaction can be carried out in the presence of a catalyst, such as a lithium compound. Examples of lithium compounds include lithium alkoxides such as lithium methoxide and ethoxide lithium; lithium halide such as lithium chloride, and lithium hydroxide. The amount of catalyst to be used is not particularly limited and is usually from about 0.0005 to 0.5 mol with respect to 1 mol dumenigo connection (2).

Temperature is the tour of the reaction, in the case of malonic acid halide, in which Z means a halogen atom, as a compound of malonic acid (4) is usually from about -30 to 100°C, preferably about -10 to 50°C. In this case, to capture a by-product, hydrogen halide, preferably the reaction is carried out in the presence of a base such as triethylamine.

Vzamodeystviya optically active amerosport (3) and the compound of malonic acid (4) gives optically active diamine connection (2), and is optically active diamine compound (2) can be isolated by adding water to the reaction mixture to conduct extraction processing, followed by concentrating the obtained organic layer. Additionally, the resulting reaction mixture containing optically active diamine connection (2), as such, can be brought into contact with the above Lewis acid, to obtain the optically active compound bisoxazoline (1).

Next, the following description discloses a method of obtaining optically active cyclopropane compounds represented by the formula (7):

where R6, R7, R8and R9are the same or different and independently denote a hydrogen atom, accelgroup, optionally substituted by a halogen atom, alkenyl is the Rupp, optionally substituted by a halogen atom, a substituted or unsubstituted aryl or arakalgudu, provided that when R6and R8are the same, R6and R7are different from each other; and R10means altergroup having 1-6 carbon atoms (hereafter referred to as optically active compound of cyclopropane (7)) interaction prehiring of olefin represented by the formula (5):

where R6, R7, R8and R9have the above values (hereafter referred to simply as the olefin (5)) and the complex ester diazo acetic acid represented by formula(6):

where R10has the above values (hereafter referred to as ester diazo acetic acid (6)) in the presence of a new asymmetric complex of copper obtained from optically active compounds bisoxazoline (1) according to this invention and compounds of copper.

Optically active compound bisoxazoline (1) has, as described above, two asymmetric carbon atom, and is usually used as a compound in which both asymmetric carbon atoms are in the (S) configuration or in the (R) configuration. Them appropriately chosen according to the desired optically active compound in the reaction is AI asymmetric synthesis, conducted using the compounds as the catalyst or catalyst component.

Examples of copper compounds can be monovalent or divalent copper compounds, and specific examples include triftorbyenzola copper (I), triftorbyenzola copper (II)acetate copper (I)acetate, copper (II)bromide copper (I)bromide copper (II)chloride copper (I)chloride copper (II) and hexaphosphate tetracosactide copper (I), and preferred triftorbyenzola copper (I). Copper compounds can be used alone, or two or more of them may be used in the form of a mixture.

The number of optically active compounds bisoxazoline (1), which must be used is usually from about 0.8 to 5 mol, preferably about 0.9 to 2 mol relative to 1 mol of the compounds of copper.

Optically active compound bisoxazoline (1) and a compound of copper is brought into contact with each other usually in the presence of a solvent, to obtain a new asymmetric copper complex. Examples of the solvent include halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride, aromatic hydrocarbons such as benzene, toluene and xylene. In addition, when the olefin (5) is liquid, it can be used as solvent. The amount of solvent that is due is to be used, usually from about 10 to 500 parts by weight relative to 1 part by weight of copper compounds.

Asymmetric copper complex usually get in the atmosphere of inert gas such as argon or nitrogen, and the temperature of its receipt is usually from about 0 to 100°C.

Asymmetric copper complex can be obtained by bringing into contact with each other optically active compounds bisoxazoline (1) and compounds of copper, and thus obtained an asymmetric copper complex can be isolated from the reaction mixture for use in the interaction of the olefin (5) and of ester (6) diazo acetic acid or can be used directly without isolation from the reaction mixture.

Examples of accelgroup, optionally substituted by a halogen atom, in the formula of the olefin (5) include C1-6alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl and exirgruppen, and such accelgroup, one or more hydrogen atoms are replaced by halogen atoms such as chloromethyl, vermeil, trifluoromethyl and chlorotalpa. Examples of altergroup, optionally substituted by a halogen atom include C2-6alkenyl, such as vinyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-pentenyl and 2-extirpa, and such altergroup, one or more hydrogen atoms to the x atoms substituted by halogen, such as 1-chloro-2-propenyl.

Examples of substituted or unsubstituted of airgroup include the unsubstituted airgroup (phenyl or naphthyl) and airgroup, substituted alkyl or alkoxygroup, such as phenyl, 1-naphthyl, 2-naphthyl, 2-were, 4-and were 3-ethoxyphenylurea. Examples of substituted or unsubstituted of Uralkaliy include alkyl, substituted specified substituted or unsubstituted allgroups. Specific examples include benzyl, 2-methylbenzyl, 4-methylbenzyl, 3-methoxybenzyl, 1-naphthylmethyl and 2-naphthylmethyl.

Examples of the olefin (5) include propene, 1-butene, isobutylene, 1-penten, 1-hexene, 1-octene, 4-chloro-1-butene, 2-penten, 2-hepten, 2-methyl-2-butene, 2,5-dimethyl-2,4-hexadiene, 2-chloro-5-methyl-2,4-hexadiene, 2-fluoro-5-methyl-2,4-hexadien, 1,1,1-Cryptor-5-methyl-2,4-hexadiene, 2-methoxycarbonyl-5-methyl-2,4-hexadien, 1,1-debtor-4-methyl-1,3-pentadiene, 1,1-dichloro-4-methyl-1,3-pentadiene, 1,1-dibromo-4-methyl-1,3-pentadiene, 1-chloro-1-fluoro-4-methyl-1,3-pentadiene, 1-fluoro-1-bromo-4-methyl-1,3-pentadiene, 2-methyl-2,4-hexadiene, 1-fluoro-1,1-dichloro-4-methyl-2-penten, 1,1,1-trichloro-4-methyl-3-penten, 1,1,1-tribromo-4-methyl-3-penten, 2,3-dimethyl-2-penten, 2-methyl-3-phenyl-2-butene, 2-bromo-2,5-dimethyl-4-hexene, 2-chloro-2,5-dimethyl-4-hexene and 2,5-dimethyl-6-chloro-2,4-hexadien.

C1-6altergroup in the formula of ester (6) diazo acetic acid represented, for example, the same groups listed as examples above, and examples of ester (6) diazo acetic acid include ethyl diazo acetate, n-propylitized, isopropylacetate, n-butylcyanoacrylate, isobutylacetate, tert-butylcatechol, penteledata and exercisethat.

The number of asymmetric complex of copper, which must be used, typically from about of 0.0001 to 0.05 mol, preferably of 0.0005-0.01 mol per metallic copper (mol copper) with respect to a complex ether (6) diazo acetic acid.

The amount of the olefin (5), which must be used, typically from about 1 mol or more, preferably 1.2 mol or more relative to 1 mol of ester (6) diazo acetic acid. Specific no upper limit, and when the olefin (5) is a liquid, can be used in a large excess of it to serve also as a solvent.

The interaction of the olefin (5) and of ester (6) diazo acetic acid is usually carried out by bringing into contact with each other three components, namely the asymmetric complex of copper, olefin (5) and of ester (6) diazo acetic acid, and their mixing, the order of mixing is not specifically limited. Normally ester (6) diazo acetic acid is added to a mixture of the asymmetric complex of copper and olefin (5). The reaction is usually carried out in the presence of a solvent, and examples of solvents include the halogenated hydrocarbon solvents, such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride; aliphatic hydrocarbons such as hexane, heptane and cyclohexane; aromatic hydrocarbons such as benzene, toluene and xylene, esters such as ethyl acetate. They can be used singularly or as a mixed solvent. Although the number that should be used is not specifically limited, from the point of view of the volumetric efficiency and properties of the reaction mixture, the amount is usually from about 2 to 30 parts by weight, preferably 5-20 parts by mass relative to 1 part by weight of ester (6) diazo acetic acid. The solvent can be pre-mixed with the olefin (5), complex ether (6) diazo acetic acid and/or an asymmetric complex of copper. Alternatively, as described above, when the olefin (5) is a liquid, the olefin (5) can also be used as a solvent.

The reaction of the olefin (5) and of ester (6) diazo acetic acid is usually carried out in an atmosphere of inert gas such as argon or nitrogen. Because water has a harmful effect on the reaction, preferably, the reaction is carried out by limiting the amount of water present in the reaction system, for example, by conducting the reaction in the presence of a dehydrating agent in the reaction system or by using the olefin (5) or solvent, prior is sustained fashion processed by dehydration.

The reaction temperature is usually from about -50 to 150°C, preferably -20 to 80°C.

After completion of the reaction of the optically active compound of cyclopropane (7) can be isolated, for example, by concentration of the reaction mixture. Isolated optically active compound of cyclopropane (7) may optionally be purified by conventional means of purification, such as distillation, column chromatography and the like.

Examples of the optically active compounds of cyclopropane (7) include optically active methyl-2-methylcyclohexanecarboxylic, optically active methyl 2,2-dimethylcyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2,2-dichloro-1-ethynyl)cyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2,2,2-trichlorethyl)cyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2,2,2-tribromoethyl)cyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2,2-dibromo-1-ethynyl)cyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2,2-debtor-1-ethynyl)cyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2-fluoro-2-chloro-1-ethynyl)cyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2-fluoro-2-bromo-1-ethynyl)cyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2-fluoro-1-propenyl)CEC is propanecarboxylate, optically active methyl 2,2-dimethyl-3-(2-chloro-1-propenyl)cyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2-chloro-2,2,2-cryptomaterial)cyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2-methoxycarbonyl-1-propenyl)cyclopropanecarboxylate, optically active methyl 2,2-dimethyl-3-(2-chloro-2-methyl)propylcyclohexyl, optically active methyl 2,2-dimethyl-3-(2-bromo-2-methyl)propylcyclohexyl and optically active methyl 2,2-dimethyl-3-(1-propenyl)propylcyclohexyl, and compounds in which the above methylgroup in the ester part of the molecule is substituted by ethyl, n-propylene, isopropyl, isobutyl and tert-bootrom in the ester part of the molecule.

Optically active compound of cyclopropane (7) can be converted into optically active cyclopropanecarbonyl acid, in which R10means a hydrogen atom by hydrolysis in accordance with the known method of hydrolysis.

Optically active amerosport represented by the formula (3)includes optically active amerosport, represented by the following formula (30):

where R31, R32, R33and R34are the same or different and independently denote a hydrogen atom, a C1-6altergroup or C1-6alkoxygroup; R35means C1-6altergroup substituted or unsubstituted panelgroup or substituted or unsubstituted arakalgudu, or two R35together with the carbon atom to which they are attached, form a ring; and * means an asymmetric carbon atom (hereafter referred to as optically active amerosport (30)). The following description is an explanation of the connection.

In the formula (30), examples of C1-6altergroup represented by R31-R35include altergroup straight or branched chain such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl and n-exirgruppen. Examples of C1-6alkoxygroup represented by R31-R34include alkoxygroup straight or branched chain, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentyloxy and n-hexyloxy.

Substituted or unsubstituted phenylpropoxy represented by R35that is, for example, the unsubstituted panelgroup, and replaced by phenylpropoxy is, for example, failgroup, replaced the above C1-6accelgroup, such as 3-and 4 were-methylphenidate, and panelgroup, replaced the above C1-6alkoxygroup, such as 2-methoxyphenyl, 3-methoxyphenyl and 4-methoxyphenyl. Substituted or unsubstituted arlbergpass is, for example, C1-6accelgroup, replaced by allgroups, such as the above substituted or unsubstituted who enil and aftercrop. Specific examples include benzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 1-naphthylmethyl and 2-naphthylmethyl.

In addition, when two R35together with the carbon atom to which they are attached, form a ring, specific examples of the ring include a ring having 3 to 7 carbon atoms, such as cyclopropane ring, ring cyclopentane, the cyclohexyl ring and the ring Cycloheptane.

Examples of optically active amerosport (30) include (R)-1-amino-1-(1-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(4-fluoro-1-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(2-methyl-1-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(4-methyl-1-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(2-methoxy-1-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(2-ethoxy-1-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(4-methoxy-1-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(2,4-dimethoxy-1-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(2-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(7-methyl-2-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(1-n-propyl-2-naphthyl)-2-methyl-2-propanol, (R)-1-amino-1-(6-methoxy-2-naphthyl)-2-methyl-2-propanol and (R)-1-amino-1-(3,8-dimethoxy-2-naphthyl)-2-methyl-2-propanol; and such compounds in which 2-methyl-2-propanol substituted groups 2-ethyl-2-butanol, 2-n-propyl-2-pentanol, 2-n-butyl-2-hexanol, 2-isobutyl-4-methyl-2-pentanol, 2-n-pentyl-2-heptanol, 2-benzyl-3-phenyl-2-propanol, 2-(3-methyl shall ensil)-3-(3-were)-2-propanol, 2-(2-methylbenzyl)-3-(2-were)-2-propanol, 2-(4-methylbenzyl)-3-(4-were)-2-propanol, 2-(2-methoxybenzyl)-3-(2-methoxyphenyl)-2-propanol, 2-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-propanol, 2-(4-methoxybenzyl)-3-(4-methoxyphenyl)-2-propanol, 2-(1-naphthylmethyl)-3-(1-naphthyl)-2-propanol and 2-(2-naphthylmethyl)-3-(2-naphthyl)-2-propanol.

Additionally, his examples also include (R)-2-amino-2-(1-naphthyl)-1,1-diphenylethanol, (R)-2-amino-2-(1-naphthyl)-1,1-di(3-were)ethanol, (R)-2-amino-2-(1-naphthyl)-1,1-di(4-were)ethanol, (R)-2-amino-2-(1-naphthyl)-1,1-di(2-methoxyphenyl)ethanol, (R)-2-amino-2-(1-naphthyl)-1,1-di(3-methoxyphenyl)ethanol, (R)-2-amino-2-(1-naphthyl)-1,1-di(4-methoxyphenyl)ethanol, 1-[(R)-amino-(1-naphthyl)methyl]cyclopropane, 1-[(R)-amino-(1-naphthyl)methyl]Cyclopentanol and 1-[(R)-amino-(1-naphthyl)methyl]cycloheptanol, and such compounds in which 1-aftercrop associated with the carbon atom that is attached to the amino group substituted by the groups of 4-fluoro-1-naphthyl, 2-methyl-1-naphthyl, 4-methyl-1-naphthyl, 2-methoxy-1-naphthyl, 2-ethoxy-1-naphthyl, 4-methoxy-1-naphthyl, 2,4-dimethoxy-1-naphthyl, 2-naphthyl, 7-methyl-2-naphthyl, 1-n-propyl-2-naphthyl, 6-methoxy-2-naphthyl and 3,8-dimethoxy-2-naphthyl.

Additional examples are such compounds in which the (R) configuration is changed to the (S) configuration.

Optically active amerosport (30) can be obtained by the optical separation of neftianogo alcohol, presents the following is armoloy (40):

where R31, R32, R33R34and R35have the above values (hereafter referred to simply as nattily alcohol (40)), using the optically active N-formylphenylboronic.

Examples of amerosport (40) include 1-amino-1-(1-naphthyl)-2-methyl-2-propanol, 1-amino-1-(4-fluoro-1-naphthyl)-2-methyl-2-propanol, 1-amino-1-(2-methyl-1-naphthyl)-2-methyl-2-propanol, 1-amino-1-(4-methyl-1-naphthyl)-2-methyl-2-propanol, 1-amino-1-(2-methoxy-1-naphthyl)-2-methyl-2-propanol, 1-amino-1-(2-ethoxy-1-naphthyl)-2-methyl-2-propanol, 1-amino-1-(4-methoxy-1-naphthyl)-2-methyl-2-propanol, 1-amino-1-(2,4-dimethoxy-1-naphthyl)-2-methyl-2-propanol, 1-amino-1-(2-naphthyl)-2-methyl-2-propanol, 1-amino-1-(7-methyl-2-naphthyl)-2-methyl-2-propanol, 1-amino-1-(1-n-propyl-2-naphthyl)-2-methyl-2-propanol, 1-amino-1-(6-methoxy-2-naphthyl)-2-methyl-2-propanol and 1-amino-1-(3,8-dimethoxy-1-naphthyl)-2-methyl-2-propanol, and such compounds in which 2-methyl-2-propanol substituted groups 2-ethyl-2-butanol, 2-n-propyl-2-pentanol, 2-n-butyl-2-hexanol, 2-isobutyl-4-methyl-2-pentanol, 2-n-pentyl-2-heptanol, 2-benzyl-3-phenyl-2-propanol, 2-(3-methylbenzyl)-3-(3-were)-2-propanol, 2-(2-methylbenzyl)-3-(2-were)-2-propanol, 2-(4-methylbenzyl)-3-(4-were)-2-propanol, 2-(2-methoxybenzyl)-3-(2-methoxyphenyl)-2-propanol, 2-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-propanol, 2-(4-methoxybenzyl)-3-(4-methoxyphenyl)-2-propanol, 2-(1-naphthylmethyl-3-(1-naphthyl)-2-propanol and 2-(2-naphthylmethyl)-3-(2-naphthyl)-2-propanol.

Examples include 2-amino-2-(1-naphthyl)-1,1-diphenylethanol, 2-amino-2-(1-naphthyl)-1,1-di(3-were)ethanol, 2-amino-2-(1-naphthyl)-1,1-di(4-were)ethanol, 2-amino-2-(1-naphthyl)-1,1-di(2-methoxyphenyl)ethanol, 2-amino-2-(1-naphthyl)-1,1-di(3-methoxyphenyl)ethanol, 2-amino-2-(1-naphthyl)-1,1-di(4-methoxyphenyl)ethanol, 1-[(amino)-(1-naphthyl)methyl]cyclopropane, 1-[(amino)-(1-naphthyl)methyl]Cyclopentanol and 1-[(amino)-(1-naphthyl)methyl]cycloheptanol, and such compounds in which 1-aftercrop associated with the carbon atom that is attached to the amino group substituted by the groups of 4-fluoro-1-naphthyl, 2-methyl-1-naphthyl, 4-methyl-1-naphthyl, 2-methoxy-1-naphthyl, 2-ethoxy-1-naphthyl, 4-methoxy-1-naphthyl, 2,4-dimethoxy-1-naphthyl, 2-naphthyl, 7-methyl-2-naphthyl, 1-n-propyl-2-naphthyl, 6-methoxy-2-naphthyl and 3,8-dimethoxy-2-naphthyl.

As amerosport (40) can be generally used racemic mixture along with a mixture of optical isomers with low optical purity, in which one of the optical isomers is present in excess relative to the other.

Optically active N-formylphenylboronic has two optical isomers, R-isomer and S-isomer, and they can be appropriately selected according to the desired optically active aminoalcohols. The number that should be used is usually from 0.1 to 1 mol relative to 1 mol of amerosport (40).

The reaction amerosport (40) and pricheski active N-formylphenylboronic usually spend their mixing in a solvent, and the order of mixing is not specifically limited. It is preferable to add the optically active N-formylphenylboronic to a solution of amerosport (40) in a solvent. Optically active N-formylphenylboronic can be added continuously or intermittently. In addition, optically active N-formylphenylboronic can be used as such or in the form of a solution in a solvent.

Examples of the solvent include aromatic hydrocarbon solvents such as toluene, xylene and chlorobenzene; solvents are ethers, such as diethyl simple ether, methyl tert-butyl simple ether, tetrahydrofuran, dioxane and dimethoxyethane; alcohol solvents such as methanol, ethanol and isopropanol; ester solvents such as ethyl acetate; the solvents are NITRILES, such as acetonitrile, and water. They can be used separately or as a mixed solvent. Of these solvents, preferred solvents are ethers, alcohol solvents and mixed solvent with water. The amount of solvent that must be used is usually from 0.5 to 100 parts by weight, preferably from 1 to 50 parts by mass relative to 1 part by weight of amerosport (40). The solvent may be added previously to aminopyrido or optically active N-formylphenylboronic.

Temperature is the tour of the reaction is usually in the range of 0° C to the boiling point with the return of phlegmy reaction mixture.

After completion of the reaction are formed diastereomeric salt of optically active N-formylphenylboronic and optically active amerosport (30) (hereafter referred to simply as diastereomer salt), and is usually part of one diastereomeric salt precipitates in the reaction mass. It can be isolated as such or, preferably, cooling or concentrating the reaction mixture to precipitate a greater number diastereomeric salt. Depending on conditions diastereomer salt is completely dissolved in the reaction mass, and, in this case, the reaction mass may be cooled or concentrated to secretariaat and highlight diastereomer salt. One of the besieged diastereomeric salt can be easily separated by ordinary filtration. Selected diastereomeric salt can be further purified, for example, processing by recrystallization.

Examples diastereomeric salt thus obtained include diastereomer salt of optically active 1-amino-(1-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(4-fluoro-1-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(2-IU the Il-1-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(4-methyl-1-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(2-methoxy-1-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(2-ethoxy-1-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(4-methoxy-1-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(2,4-dimethoxy-1-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(2-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(7-methyl-2-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(1-n-propyl-2-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(6-methoxy-2-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-amino-1-(3,8-dimethoxy-2-naphthyl)-2-methyl-2-propanol and optically active N-formylphenylboronic is a and such diastereomer salt, in which group 2-methyl-2-propanol substituted groups 2-ethyl-2-butanol, 2-n-propyl-2-pentanol, 2-n-butyl-2-hexanol, 2-isobutyl-4-methyl-2-pentanol, 2-n-pentyl-2-heptanol, 2-benzyl-3-phenyl-2-propanol, 2-(3-methylbenzyl)-3-(3-were)-2-propanol, 2-(2-methylbenzyl)-3-(2-were)-2-propanol, 2-(4-methylbenzyl)-3-(4-were)-2-propanol, 2-(2-methoxybenzyl)-3-(2-methoxyphenyl)-2-propanol, 2-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-propanol, 2-(4-methoxybenzyl)-3-(4-methoxyphenyl)-2-propanol, 2-(1-naphthylmethyl)-3-(1-naphthyl)-2-propanol and 2-(2-naphthylmethyl)-3-(2-naphthyl)-2-propanol.

Examples also include diastereomer salt of optically active 2-amino-2-(1-naphthyl)-1,1-diphenylethanol and optically active N-formylphenylboronic, diastereomer salt of optically active 2-amino-2-(1-naphthyl)-1,1-di(3-were)ethanol and optically active N-formylphenylboronic, diastereomer salt of optically active 2-amino-2-(1-naphthyl)-1,1-di(4-were)ethanol and optically active N-formylphenylboronic, diastereomer salt of optically active 2-amino-2-(1-naphthyl)-1,1-di(2-methoxyphenyl)ethanol and optically active N-formylphenylboronic, diastereomer salt of optically active 2-amino-2-(1-naphthyl)-1,1-di(3-methoxyphenyl)ethanol and optically active N-formylphenylboronic, diastereomer salt of optically active 2-amino-2-(1-naphthyl)-1,1-di(4-methoxyphenyl)ethanol and optically active N-is armillariella, diastereomer salt of optically active 1-[(amino)-(1-naphthyl)methyl]cyclopropanol and optically active N-formylphenylboronic, diastereomer salt of optically active 1-[(amino)-(1-naphthyl)methyl]Cyclopentanol and optically active N-formylphenylboronic and diastereomer salt of optically active 1-[(amino)-(1-naphthyl)methyl]cycloheptanol and optically active N-formylphenylboronic and such compounds in which 1-aftercrop associated with the carbon atom that is attached to the amino group of the optically active alcohols naftalovich forming these respective diastereomeric salts, substituted groups 4-fluoro-1-naphthyl, 2-methyl-1-naphthyl, 4-methyl-1-naphthyl, 2-methoxy-1-naphthyl, 2-ethoxy-1-naphthyl, 4-methoxy-1-naphthyl, 2,4-dimethoxy-1-naphthyl, 2-naphthyl, 7-methyl-2-naphthyl, 1-n-propyl-2-naphthyl, 6-methoxy-2-naphthyl and 3,8-dimethoxy-2-naphthyl.

Diastereomer salt, thus obtained, can easily be converted into optically active amerosport (30), as such or after purification by washing, recrystallization, etc. with subsequent alkali treatment.

Alkaline treatment can usually be carried out by mixing diastereomeric salt and alkali, and the temperature of mixing is usually in the range from 0 to 100°C. Examples of alkali, which should be used include hydroxides of alkali metals such as potassium hydroxide and g is droxia sodium, and typically use their aqueous solution. When using aqueous alkaline solution, the concentration of alkali is usually from 1 to 50% by weight, preferably from 3 to 20% by weight. The amount of alkali that must be used, typically from about 1 to 5 mol relative to 1 mol diastereomeric salt.

When diastereomer salt is subjected to alkaline treatment, usually optically active amerosport (30) is separated as a layer of oil or precipitated as solids of the mass after the alkali treatment, and optically active amerosport (30) can be isolated as such or optically active amerosport (30) can be isolated by adding water-insoluble organic solvent to the weight after the alkali treatment for the extraction and distillation of the organic solvent from the obtained organic layer. Examples of water-insoluble organic solvent include solvents are ethers, such as diethyl simple ether and methyl tert-butyl simple ether; ester solvents such as ethyl acetate; aromatic hydrocarbon solvents such as toluene, xylene and chlorobenzene; halogenated hydrocarbon solvents such as dichloromethane and chloroform, and the number that must be used, typically in the range from 0.5 to 50 parts by mass relative to 1 part by mass, the use of which has been created diastereomeric salt. Water-insoluble organic solvent may be added in advance at the time of the alkali treatment diastereomeric salt.

Optically active amerosport (30) can also be selected pretreatment diastereomeric salt acid and subsequent alkaline treatment. When diastereomer salt pre-treated with acid, optically active N-formylphenylboronic outstanding. Then, preferably, the alkaline treatment is carried out after separation of the released optically active N-formylphenylboronic.

Acid treatment is generally carried out by mixing diastereomeric salt and an aqueous acid solution, and the temperature of mixing is usually 0 to 100°C. the acid is usually used an aqueous solution of mineral acid, such as chloromethane acid, sulfuric acid and phosphoric acid, and the concentration is usually from 1 to 50% by weight, preferably from 5 to 40% by weight. The amount of acid that must be used is usually from 1 to 5 mol, preferably 1-2 mol relative to 1 mol diastereomeric salt.

The separation method released optically active N-formylphenylboronic is, for example, a method of extracting it by adding a water-insoluble organic solvent to the mass, in which diastereomer salt previously subjected to the acid treatment. Such water-insoluble organic solvents include, for example, those solvents described above, and the number that must be used is usually from 0.5 to 20 parts by weight per 1 part by weight used diastereomeric salt. Water-insoluble organic solvent does not cause problems even when it first add during the acid treatment diastereomeric salt.

When released optically active N-formylphenylboronic partially or fully deposited in the mass after the acid treatment, the mass may be subjected to filtration as such or, if necessary, after further cooling to separate released optically active N-formylphenylboronic.

In the alkaline treatment after the acid treatment, using an aqueous solution of alkali metal hydroxide such as potassium hydroxide and sodium hydroxide, and the concentration of the solution is usually from 1 to 50% by weight, preferably from 5 to 20% by weight. The alkali is used in such quantity that the pH of the mass to be processed becomes 10 or higher, and treatment temperature is usually from 0 to 100°C.

When the alkaline processing diastereomeric salt is carried out after the preliminary acid treatment, optically active amerosport (30) typically separates in the form with the HHS oil or precipitated as solids in the mass after the alkali treatment and the layer of oil or solids can be isolated as such. Alternatively, optically active amerosport (30) can be isolated by adding water-insoluble organic solvent to the weight after the alkali treatment for the extraction and distillation of the organic solvent from the obtained organic layer. As the water-insoluble organic solvent is suitable, for example, the same solvents that are listed, and the number that must be used is usually from 0.5 to 50 parts by mass relative to 1 part by weight diastereomeric salt used in processing. Water-insoluble organic solvent may be added in advance at the time of the alkali treatment.

Used optically active N-formylphenylboronic can be easily extracted, and the extracted optically active N-formylphenylboronic can be reused for the reaction of amerosport (40) and optically active N-formylphenylboronic. When diastereomer salt is subjected to alkaline treatment without pre-treatment with acid, optically active N-formylphenylboronic can be removed by acid treatment of the treated mass obtained after extracting the optically active amerosport (30). When diastereomer salt is treated with alkali after pre-treatment with acid, optically active N-formylphenylboronic usually actiono or completely precipitated in the acid-treated mass, obtained by acid treatment, and the mass is filtered as such or, if necessary, after further cooling to extract the optically active N-formylphenylboronic. Alternatively, water-insoluble organic solvent is added to the acid-treated mass for extraction and organic solvent is distilled off from the obtained organic layer to extract the optically active N-formylphenylboronic. As the water-insoluble organic solvent is suitable, for example, the same solvents as above. Water-insoluble organic solvent may be added in advance at the time of acid treatment.

Amerosport (40) can be obtained by the method containing the following steps (A)-(D).

That is, (A) the interaction of compounds nafcillin represented by the formula (41):

where R31, R32, R33and R34have the above values (hereafter referred to simply as compound nafcillin (41)), with a chlorination agent and the alcohol represented by the formula (42):

where R9means C1-6accelgroup (hereafter referred to simply as alcohol (42)), to obtain the hydrochloride of ester of the amino acids represented by the formula (43):

where R31, R32, R33, R34and R9have the above values (hereafter referred to simply as the hydrochloride of ester amino acids (43)),

(B) interaction of ester hydrochloride amino acids (43)obtained at this stage (A), with the compound represented by the formula (44):

where n is 1, 2 or 3 (hereafter referred to simply as the compound (44)), or formula (45):

where n has the values indicated above, and X represents a chlorine atom, a bromine atom or an iodine atom (hereafter referred to simply as the compound (45)), in the presence of a tertiary amine, to obtain the compound represented by the formula (46):

where R31, R32, R33, R34, R9and n have the above values (hereafter referred to simply as the compound (46)),

(C) interaction of the compound (46)obtained at this stage (B), with the compound represented by the formula (47):

where R35means C1-6accelgroup, substituted or unsubstituted arakalgudu or substituted or unsubstituted panelgroup, and X' denotes a halogen atom (hereafter referred to simply as the compound (47)), or a compound represented by the formula (48):

where R35'means C2-6akilagpa, and X' has the values listed above (hereafter referred to simply as the compound (48)), with compounds represented by formula (49):

where R31, R32, R33, R34, R35and n have the above values (hereafter referred to simply as the compound (49)) and

(D) interaction of the compound (49)obtained at this stage (C), with a base, to obtain neftianogo alcohol (40).

First stage will be illustrated (A). Stage (A) is the stage of obtaining the hydrochloride of ester amino acids (5) the interaction of compounds nafcillin (41) and chlorination agent in the presence of alcohol (42).

Examples of compounds nafcillin (3) include 1-nafcillin, 2-methyl-1-nafcillin, 4-methyl-1-nafcillin, 2-methoxy-1-nafcillin, 2-ethoxy-1-nafcillin, 4-methoxy-1-nafcillin, 2,4-dimethoxy-1-nafcillin, 2-nafcillin, 7-methyl-2-nafcillin, 1-n-propyl-2-nafcillin, 6-methoxy-2-nafcillin and 3,8-dimethoxy-2-nafcillin.

Connection nafcillin (3) may be commercially available or can be obtained by the interaction of naphthaldehyde with cenocoeliinae, such as sodium cyanide, and ammonium carbonate followed by treatment of the reaction product with alkali, such as hydroxide feces is I (for example, Experimental Chemistry, 4th edition, vol. 22, p. 195, Chemical Society of Japan).

Examples of the chlorination agent include thionyl chloride and carbonylchloride, and the number that must be used is usually 1 mol or more, preferably 1.1 mol or more relative to 1 mol of compound of nafcillin (41). Specific upper limit does not exist, when it too much, it may be economically disadvantageous. Therefore, in practice the number is double with respect to 1 mol or less.

In the formula of alcohol (42) R6means C1-6accelgroup, and examples include the same groups described above. Examples of the alcohol (42) include methanol, ethanol, n-propanol, isopropanol, n-butanol, Isobutanol, sec-butanol, pentanol and hexanol.

The number of alcohol (42), which must be used is usually 1 mole or more relative to 1 mol of compound of nafcillin (41), and specific no upper limit. Alcohol can be used in large excess so that it served also as a solvent. Usually, the reaction of the compound of nafcillin (41), the chlorination agent and alcohol (42) is conducted by mixing the three reactants, and the order of mixing is not specifically limited. In addition, the reaction is usually conducted in a solvent, and examples of the solvent include aliphatic hydrocarbon solvents such as hexane and heptane; aromatic the ski hydrocarbon solvents, such as toluene, xylene and chlorobenzene; halogenated hydrocarbon solvents such as dichloromethane and chloroform; the solvents are ethers, such as diethyl simple ether, methyl tert-butyl simple ether, tetrahydrofuran, dioxane and dimethoxyethane; ester solvents such as ethyl acetate, and the solvents are NITRILES, such as acetonitrile. They can be used singularly or as a mixed solvent. As described above, the alcohol (42) can be used as solvent. The amount of solvent to be used may be such as to give the possibility to mix the reaction mass. Usually, it is 1 part by mass or more relative to 1 part by weight of compounds nafcillin (41), and specific no upper limit.

The reaction temperature is usually from 0°C to the boiling point with the return of phlegmy the reaction mixture, preferably from 10 to 60°C.

After completion of the reaction, the reaction mixture is subjected to processing by the concentration or deposition processing to highlight the hydrochloride of ester amino acids (43). Sometimes the resulting hydrochloride of ester amino acids (43) partially or completely precipitated in the reaction mixture and, in this case, the reaction mixture directly or after partial conc the cation and, if necessary, cooling filter to select the hydrochloride of ester amino acids (43). Although dedicated hydrochloride of ester amino acids (43) can be directly used in the next stage (B), it is preferable to use it after washing solvent, which almost does not dissolve the hydrochloride of ester amino acids (43), such as a specified simple solvent ether, because sometimes it contains unreacted alcohol (42) or chlorination agent.

Examples of ester hydrochloride amino acids (43)thus obtained include the hydrochloride of the methyl ester of 1-nafcillin, the hydrochloride of the methyl ester of 2-methyl-1-nafcillin, hydrochloride methyl ester 4-methyl-1-nafcillin, hydrochloride methyl ester 2-methoxy-1-nafcillin, hydrochloride methyl ester 2-ethoxy-1-nafcillin, hydrochloride methyl ester 4-methoxy-1-nafcillin, hydrochloride methyl ester 2,4-dimethoxy-1-nafcillin, hydrochloride methyl ester 2-nafcillin, hydrochloride methyl ester 7-methyl-2-nafcillin, hydrochloride methyl ester 1-n-propyl-2-nafcillin, hydrochloride methyl ester of 6-methoxy-2-nafcillin, hydrochloride methyl ester 3,8-dimethoxy-2-nafcillin and connections, where their corresponding methyl ester group substituted gr is pami ethyl ester, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether and sec-butyl ether.

Then will be illustrated stage (B). Stage (B) is the stage of obtaining compound (46) the interaction of ester hydrochloride amino acids (43)obtained at this stage (A), or compound (44)or the compound (45) in the presence of a tertiary amine.

In the formula of the compound (44) n is 1, 2 or 3. Examples of the compound (6) include triperoxonane anhydride, 2,2,3,3,3-pentafluoropropionic anhydride, 2,2,3,3,4,4,4-getattributenames anhydride. In the formula of the compound (45) X represents a chlorine atom, bromine or iodine, and examples of the compound (45) include the acid chloride triperoxonane acid, acid chloride 2,2,3,3,3-pentafluoropropanol acid and the acid chloride 2,2,3,3,4,4,4-getattributenames acid. As compounds (44) and (45) can be used, for example, commercially available compounds.

The amount of compound (44) or the compound (45), which must be used, typically from 0.8 to 2 mol, preferably from 1 to 1.5 mol relative to 1 mol of ester hydrochloride amino acids (43).

Examples of the tertiary amine include triethylamine, tri-n-Propylamine, tri-n-butylamine, diisopropylethylamine, N,N-dimethylaniline, N,N-diethylaniline, pyridine and 4-(N,N-dimethylamino)pyridine. The quantity should be used in Lovano, usually from 1.5 to 3 mol, preferably from 1.8 to 2.5 mol relative to 1 mol of ester hydrochloride amino acids (43).

Usually the reaction of ester hydrochloride amino acids (43) and either connection (44)or the compound (45) is conducted by mixing the two reactants, and the order of mixing is not specifically limited. The reaction is usually conducted in a solvent, and examples of the solvent include the above aliphatic hydrocarbon solvents, aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, solvents, ethers, ester solvents and solvents NITRILES. They can be used singularly or as a mixed solvent. The number that should be used may be such as to give the possibility to mix the reaction mixture. Usually, it is 1 part by mass or more relative to 1 part by weight of ester hydrochloride amino acids (43).

The reaction temperature is usually 0°C or below, preferably -20 to -50°C.

After completion of the reaction, the reaction mixture is mixed with water and, if necessary, add water-insoluble organic solvent and spend processing extraction and the obtained organic layer is concentrated to isolate compound (46). Insulated joint 46) directly or after further purification by conventional methods of purification, such as recrystallization or column chromatography, can be used in the next stage (C).

Examples of the compound (46) include a methyl ester of N-(TRIFLUOROACETYL)-1-nafcillin, methyl ester N-(TRIFLUOROACETYL)-2-methyl-1-nafcillin, methyl ester N-(TRIFLUOROACETYL)-4-methyl-1-nafcillin, methyl ester N-(TRIFLUOROACETYL)-2-methoxy-1-nafcillin, methyl ester N-(TRIFLUOROACETYL)-2-ethoxy-1-nafcillin, methyl ester N-(TRIFLUOROACETYL)-4-methoxy-1-nafcillin, methyl ester N-(TRIFLUOROACETYL)-2,4-dimethoxy-1-nafcillin, methyl ester N-(TRIFLUOROACETYL)-2-nafcillin, methyl ester N-(TRIFLUOROACETYL)-7-methyl-2-nafcillin, methyl ester N-(TRIFLUOROACETYL)-1-n-propyl-2-nafcillin, methyl ester N-(TRIFLUOROACETYL)-6-methoxy-2-nafcillin, methyl ester N-(TRIFLUOROACETYL)-3,8-dimethoxy-2-nafcillin; connections where specified, the corresponding methyl ester group substituted by the groups ethyl ether, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether and sec-butyl ether; and compounds where triptoreline, Deputy to the amino group of these compounds, the substituted group, 2,2,3,3,3-pentafluoropropanol and 2,2,3,3,4,4,4-heptafluorobutyl.

Next stage will be illustrated (C). Stage (C) is the stage of obtaining the compound (49) interaction Conn is in (46), received on the specified stage (B), and either compound (47), or compounds (48).

In the formula of the compound (48) R35'means C2-6alkylen, and examples include ethylene, trimethylene, tetramethylene, pentamethylene and hexamethylene. Examples of the compound (47) or the compound (48) include chloride (or bromide) Metalmania, chloride (or bromide) of etermine, chloride (or bromide) n-Propylamine, chloride (or bromide) n-butylamine, chloride (or bromide) isobutylamine, chloride (or bromide) n-pentermine, chloride (or bromide) n-hexylamine, chloride (or bromide) benzylamine, chloride (or bromide) 2-methylbenzylamine, chloride (or bromide) 4-methylbenzylamine, chloride (or bromide) 2-methoxybenzylamine, chloride (or bromide) 3-methoxybenzylamine, chloride (or bromide) 4-methoxybenzylamine, chloride (or bromide) 1-naphthylethylene, chloride (or bromide) 2-naphthylethylene, chloride (or bromide) vinylmania, chloride (or bromide) 3-methylphenylamine, chloride (or bromide) 4-methylphenylamine, chloride (or bromide) 2-methoxybenzylamine, chloride (or bromide) 3-methoxybenzylamine, chloride (or bromide) 4-methoxybenzylamine, chloride (or bromide) ethylendiamine, chloride (or bromide) tetramethylaniline and chloride (or bromide) hexamethylendiamine. As the compound (47) or the compound (48) can be used commercially available compounds, or they mouthbut obtained by the interaction of the corresponding compounds of halogen and metal magnesium.

The number that should be used in case of application of the compound (47), usually from 2 to 3 mol, preferably from 2.1 to 2.7 mol relative to 1 mol of compound (46). The number that should be used in case of application of the compound (48), usually 1 to 1.5 mol, preferably 1.1 to 1.4 mol relative to 1 mol of compound (46).

Usually the reaction of the compound (46) or the compound (47)or the compound (48) is conducted by mixing the two reagents in the solvent, and the order of mixing is not specifically limited. Examples of the solvent include the solvents are ethers, such as diethyl ether, and the number that must be used is usually from 1 to 50 parts by weight, preferably from 3 to 20 parts by mass relative to 1 part by mass of compound (46). If necessary, these aromatic hydrocarbon solvents such as toluene, can be added to it.

The reaction temperature is usually from -20°C to the boiling point with the return of phlegmy the reaction mixture, preferably from -10 to 30°C.

After completion of the reaction the reaction mixture and the aqueous solution of mineral acid, such as chloromethane acid, sulfuric acid or phosphoric acid, are mixed to be processed by extraction and the obtained organic layer is concentrated to isolate compound (49). The separation of the TES compound (49) directly or after further purification by conventional methods of purification, such as recrystallization or column chromatography, can be used in the next stage (D).

Examples of the compound (49)thus obtained include 1-(triptorelin)-(1-naphthyl)-2-methyl-2-propanol, 1-(triptorelin)-1-(4-fluoro-1-naphthyl)-2-methyl-2-propanol, 1-(triptorelin)-1-(2-methyl-1-naphthyl)-2-methyl-2-propanol, 1-(triptorelin)-1-(4-methyl-1-naphthyl)-2-methyl-2-propanol,1-(triptorelin)-1-(2-methoxy-1-naphthyl)-2-methyl-2-propanol, 1-(triptorelin)-1-(2-ethoxy-1-naphthyl)-2-methyl-2-propanol,

1-(triptorelin)-1-(4-methoxy-1-naphthyl)-2-methyl-2-propanol,

1-(triptorelin)-1-(2,4-dimethoxy-1-naphthyl)-2-methyl-2-propanol,

1-(triptorelin)-1-(2-naphthyl)-2-methyl-2-propanol, 1-(triptorelin)-1-(7-methyl-2-naphthyl)-2-methyl-2-propanol,

1-(triptorelin)-1-(1-n-propyl-2-naphthyl)-2-methyl-2-propanol,

1-(triptorelin)-1-(6-methoxy-2-naphthyl)-2-methyl-2-propanol,

1-(triptorelin)-1-(3,8-dimethoxy-2-naphthyl)-2-methyl-2-propanol; join where group 2-methyl-2-propanol of the above compounds is replaced by groups of 2-ethyl-2-butanol, 2-n-propyl-2-pentanol, 2-n-butyl-2-hexanol, 2-isobutyl-4-methyl-2-pentanol, 2-n-pentyl-2-heptanol, 2-benzyl-3-phenyl-2-propanol, 2-(3-methylbenzyl)-3-(3-were)-2-propanol, 2-(2-methylbenzyl)-3-(2-were)-2-propanol, 2-(4-methylbenzyl)-3-(4-were)-2-propanol,

2-(2-marks benzyl)-3-(2-methoxyphenyl)-2-propanol,

2-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-propanol,

2-(4-methoxybenzyl)-3-(4-methoxyphenyl)-2-propanol,

2-(1-naphthylmethyl)-3-(1-naphthyl)-2-propanol,

2-(2-naphthylmethyl)-3-(2-naphthyl)-2-propanol, and compounds, where triptoreline the above compounds substituted groups 2,2,3,3,3-pentafluoropropanol and 2,2,3,3,4,4,4-heptafluorobutyrate.

Additionally, its examples include 2-(triptorelin)-2-(1-naphthyl)-1,1-diphenylethanol, 2-(triptorelin)-2-(1-naphthyl)-1,1-di(3-were)ethanol, 2-(triptorelin)-2-(1-naphthyl)-1,1-di(4-were)ethanol, 2-(triptorelin)-2-(1-naphthyl)-1,1-di(2-methoxyphenyl)ethanol

2-(triptorelin)-2-(1-naphthyl)-1,1-di(3-methoxyphenyl)ethanol

2-(triptorelin)-2-(1-naphthyl)-1,1-di(4-methoxyphenyl)ethanol

1-[(triptorelin)-(1-naphthyl)methyl]cyclopropane, 1-[(triptorelin)-(1-naphthyl)methyl]Cyclopentanol, 1-[(triptorelin)-(1-naphthyl)methyl]cycloheptanol and connections, where 1-aftercrop associated with the carbon atom to which is attached triptoreline the above compounds, the substituted groups of 4-fluoro-1-naphthyl, 2-methyl-1-naphthyl, 4-methyl-1-naphthyl, 2-methoxy-1-naphthyl, 2-ethoxy-1-naphthyl, 4-methoxy-1-naphthyl, 2,4-dimethoxy-1-naphthyl, 2-naphthyl, 7-methyl-2-naphthyl, 1-n-propyl-2-naphthyl, 6-methoxy-2-naphthyl and 3,8-dimethoxy-2-naphthyl.

And finally be revealed stage receiving the monosperma (40) by the interaction of the compound (49), received on the specified stage (C), to the base.

Examples of the base include hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide, hydroxides of alkaline earth metals such as calcium hydroxide and barium hydroxide, and usually use their aqueous solutions. The number of bases that must be used, usually 1-3 mol, preferably from 1.2 to 2.5 mol relative to 1 mol of compound (49). Usually the reaction of the compound (49) and the base is carried out in a solvent, and examples of the solvent include the above alcohol solvents, water and mixed solvents of water and alcoholic solvents. The number that must be used, usually from 2 to 30 parts by weight, preferably from 3 to 15 parts by weight relative to 1 part by mass of compound (49).

The reaction temperature is usually from 0°C to the boiling point with the return of phlegmy the reaction mixture, preferably from 10 to 60°C.

After completion of the reaction, for example, the reaction mixture was concentrated and then mixed with water-insoluble organic solvent for the extraction and processing of the obtained organic layer is concentrated to isolate amerosport (40). Examples of water-insoluble organic solvent include the same solvents as those described above. Selected amines the RTI (40) can be further purified by conventional methods of purification, such as recrystallization or column chromatography.

Industrial applicability

The use of an asymmetric complex of copper obtained from the new optically active compounds bisoxazoline according to this invention and compounds of copper gives the opportunity to obtain optically active compound of cyclopropane with good diastereoselectivity and enantioselectivity at a high yield and, therefore, this invention is more advantageous from the industrial point of view.

Examples

The invention will be further disclosed in detail in the examples. This invention is not limited to these examples.

Example 1

In nitrogen atmosphere 1.2 g (S)-1-amino-1-(1-naphthyl)-2-methyl-2-propanol, and 0.37 g of diethylmalonate and 70 ml of xylene is subjected to reaction by mixing and stirring at an internal temperature of 130°C for 5 hours to obtain a reaction mixture containing N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]propane-1,3-diamide. 79 mg of tetraisopropoxide titanium is added to the reaction mixture and the mixture was stirred at an internal temperature of 130°C for 48 hours to effect the reaction. After completion of the reaction, the reaction mixture was concentrated and the concentrated residue is purified column chromatography (neutral alumina, chloroform), is the learn 0.7 g of white powder of bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]methane (yield: 54%).

1H-NMR data of bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]methane (δ: ppm, solvent CDCl3, TMS standard)

0,84 (s, 6H), is 1.82 (s, 6H), of 3.69 (s, 2H), of 5.81 (s, 2H), 7,43-to 7.59 (m, 8H), 7,75-to 7.95 (m, 6H).

Example 2

In the same manner as described in example 1, except that 1.2 g (S)-1-amino-1-(2-naphthyl)-2-methyl-2-propanol is used instead of 1.2 g (S)-1-amino-1-(1-naphthyl)-2-methyl-2-propanol get 0,79 g of pale yellow powder bis[2-[(4S)-(2-naphthyl)-5,5-dimethyloxazole]]methane (yield: 61%).

1H-NMR data of bis[2-[(4S)-(2-naphthyl)-5,5-dimethyloxazole]]methane (δ: ppm, solvent CDCl3, TMS standard)

to 0.92 (s, 6H), 1.69 in (s, 6H), 3,63 (s, 2H), 5,10 (s, 2H), 7,40-of 7.48 (m, 6H), 7,70-7,83 (m, 8H).

Example 3

In nitrogen atmosphere mix 2 g of (S)-1-amino-1-(1-naphthyl)-2-methyl-2-propanol, 1.1 g of triethylamine (digidrirovanny) and 17 ml of dichloromethane (digidrirovanny) and then cooled to an internal temperature -10°C. 0.8 g of acid chloride of dimethylmaleic acid is added dropwise to this for 3 minutes and the resulting mixture was warmed to room temperature. The mixture is stirred for 6 hours to carry out reaction. After completion of the reaction to it was added 20 ml of aqueous saturated solution of ammonium chloride to separate into layers. The obtained organic layer was washed with three times 25 ml of water and concentrate. The concentrated residue is dried under reduced pressure, the research Institute at an internal temperature of 40° C, obtaining 2.5 g of N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-DIMETHYLPROPANE-1,3-diamide (yield: 100%).

1H-NMR data of N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-DIMETHYLPROPANE-1,3-diamide (δ: ppm, the solvent CD3OD, TMS standard)

of 0.90 (s, 6H), of 1.36 (s, 6H), of 1.46 (s, 6H), is 4.85 (s, 4H), vs. 5.47 (s, 2H), 7,13 (t, J=9.0 Hz, 2H), 7,33-7,35 (m, 2H), 7,45-7,52 (m, 4H), of 7.70 (d, J=9.0 Hz, 2H), 7,83-7,86 (m, 2H), 8,29 (d, J=9.0 Hz, 2H).

1.8 g of N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-DIMETHYLPROPANE-1,3-diamide, thus obtained, and 90 ml of xylene are mixed and stirred by a stirrer at an internal temperature of 130°C for 1 hour. Then added to the mixture of 97 mg of tetraisopropoxide titanium and the mixture is stirred at the same temperature for 48 hours to effect the reaction. After completion of the reaction, the reaction mixture was concentrated and the concentrated residue is purified column chromatography (neutral alumina, hexane/ethyl acetate = 10/1 by volume)to give 1.4 g of a white powder of 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]propane (yield: 83%).

1H-NMR data of 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]propane (δ: ppm, solvent CDCl3, TMS standard)

0,81 (s, 6H), of 1.78 (s, 6H), is 1.81 (s, 6H), to 5.85 (s, 2H), 7,39-of 7.55 (m, 8H), of 7.75 (d, J=9.0 Hz, 2H), 7,87 (d, J=9.0 Hz, 2H), 7,94 (d, J=9.0 Hz, 2H).

Example 4

In the atmosphere of nitrogen is mixed with 1.5 g of (S)-1-amino-1-(2-naphthyl)-2-methyl-2-propanol, 0.84 g of triethylamine (on the hydrated) and 13 ml of dichloromethane (digidrirovanny) and then cooled to an internal temperature -10° C. To this is added dropwise 0.6 g of dichlorohydrin dimethylmaleic acid for 3 minutes. The resulting mixture was warmed to room temperature. The mixture was stirred as such for 7 hours to effect the reaction. After completion of the reaction to it was added 20 ml of aqueous saturated solution of ammonium chloride to separate into layers. The obtained organic layer was washed with three times 25 ml of water and concentrate. The concentrated residue is dried under reduced pressure at an internal temperature of 40°C, obtaining 1.8 g of N,N'-bis[(1S)-(2-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-DIMETHYLPROPANE-1,3-diamide (yield: 100%).

1H-NMR data of N,N'-bis[(1S)-(2-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-DIMETHYLPROPANE-1,3-diamide (δ: ppm, the solvent CD3OD, TMS standard)

to 1.00 (s, 6H), of 1.30 (s, 6H), of 1.50 (s, 6H), a 4.86 (s, 4H), to 4.87 (s, 2H), 7,27 was 7.45 (m, 8H), 7,66-of 8.06 (m, 6H).

1.8 g of N,N'-bis[(1S)-(2-naphthyl)-2-hydroxy-2-methylpropyl]-2,2-DIMETHYLPROPANE-1,3-diamide, thus obtained, and 90 ml of xylene are mixed and stirred by a stirrer at an internal temperature of 130°C for 1 hour. Then to the reaction mixture are added 97 mg tetraisopropoxide titanium and the mixture is stirred at the same temperature for 48 hours to effect the reaction. After completion of the reaction, the reaction mixture was concentrated and the concentrated residue is purified column chromatography (neutral is hydrated aluminum oxide, hexane/ethyl acetate = 5/1 by volume)to give 1.3 g of white powder of 2,2-bis[2-[(4S)-(2-naphthyl)-5,5-dimethyloxazole]]propane (yield: 77%).

1H-NMR data of 2,2-bis[2-[(4S)-(2-naphthyl)-5,5-dimethyloxazole]]propane (δ: ppm, solvent CDCl3, TMS standard)

of 0.90 (s, 6H), of 1.66 (s, 6H), to 1.76 (s, 6H), of 5.05 (s, 2H), 7,34-7,46 (m, 6H), 7,66-with 8.05 (m, 8H).

Example 5

In the atmosphere of nitrogen is mixed with 1.5 g of (S)-1-amino-1-(1-naphthyl)-2-methyl-2-propanol, 0.84 g of triethylamine (digidrirovanny) and 13 ml of dichloromethane (digidrirovanny) and then cooled to an internal temperature -10°C. Then 0,58 g dichlorohydrin 1,1-cyclopropanedicarboxylic acid is added dropwise within 3 minutes and the resulting mixture was warmed to room temperature. The mixture is stirred for 7 hours to effect the reaction. After completion of the reaction, there is added 20 ml of aqueous saturated solution of ammonium chloride to separate into layers. The obtained organic layer was washed with three times 25 ml of water and concentrate. The concentrated residue is dried under reduced pressure at an internal temperature of 40°C, receiving of 1.9 g of N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]cyclopropane-1,1-dicarboxamide (yield: 100%).

1H-NMR data of N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]cyclopropane-1,1-dicarboxamide (δ: ppm, the solvent CD3OD, TMS standard)

to 0.97 (s, 6H), 1.0 to a 1.08 (m, 2H), 1.32 to about 1.35 (m, 2H), of 1.35 (s, 6H, to 4.87 (s, 4H), 5,86 (s, 2H), 7,32-rate of 7.54 (m, 8H), 7,76 (d, J=9.0 Hz, 2H), a 7.85 (d, J=9.0 Hz, 2H), 8,31 (d, J=9.0 Hz, 2H).

to 1.83 g of N,N'-bis[(1S)-(1-naphthyl)-2-hydroxy-2-methylpropyl]cyclopropane-1,1-dicarboxamide, thus obtained, 100 ml of xylene are mixed and stirred by a stirrer at an internal temperature of 130°C for 1 hour and then the reaction mixture are added 99 mg tetraisopropoxide titanium. The mixture is stirred at the same temperature for 40 hours to complete the reaction. After completion of the reaction, the reaction mixture was concentrated and the concentrated residue is purified column chromatography (silica gel, hexane/ethyl acetate = 4/1 by volume)to give 1.23 g blignault powder 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]cyclopropane (yield: 72%).

1H-NMR data of 1,1-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]cyclopropane (δ: ppm, solvent CDCl3, TMS standard)

of 0.83 (s, 6H), 1,53-to 1.61 (m, 2H), 1,69 is 1.75 (m, 2H), 1.77 in (s, 6H), USD 5.76 (s, 2H), 7,46-rate of 7.54 (m, 8H), 7,78 (d, J=9.0 Hz, 2H), 7,86-7,94 (m, 4H).

Example 6

In a 50 ml vessel Slanka, nitrogen purged, 27 mg of 2,2-bis[2-[(4S)-(1-naphthyl)-5,5-dimethyloxazole]]propane obtained in example 3, is added to the white suspension containing 18 mg triftoratsetata copper (I) and 5 ml of dichloroethane, and the resulting mixture was stirred at room temperature for 10 minutes, getting blue homogeneous solution containing an asymmetric copper complex Then this type of 7.8 g of 2,5-dimethyl-2,4-hexadiene and the internal temperature is brought to 40° C. 1.1 g of ethyl diazo acetate is added dropwise to this for 2 hours and the resulting mixture was stirred at the same temperature for 30 minutes to effect the reaction. The reaction mixture was analyzed by gas chromatography, revealing obtaining ethyl-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate with 93% yield based on ethyl diazo acetate) and the ratio of TRANS-isomer/CIS-isomer = 69/31. Optical purity analyze liquid chromatography, finding that the optical purity of the TRANS-isomer 82% e.e. and the CIS isomer 8% e.e. In this context, TRANS-isomer means the compound having ester group in position 1 and 2-methyl-1-propylgroup in position 3 on the opposite side with respect to the plane of the cyclopropane ring, and a CIS-isomer means the compound having ester group in position 1 and 2-methyl-1-propylgroup in position 3 on the same side (hereafter the same in the following examples).

Example 7

In the same manner as described in example 6, tert-butyl-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate get with exit 92% (based on tert-butylcyanoacrylate) except that 1.4 g of tert-butyldiethanolamine used instead of 1.1 g of ethyl diazo acetate. The ratio of TRANS-isomer/CIS-isomer 87/13. The reaction mixture is concentrated and a portion 1 g of the obtained concentrated residue from eraut. To this add 0.1 ml triperoxonane acid and 5 ml of toluene and the resulting mixture was stirred at an internal temperature of 100°C for 3 hours to complete the reaction and obtain 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarbonyl acid. The obtained 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarbonyl acid is subjected to reaction with 1-menthol and the obtained 1-metalowy ester analyzed by gas chromatography, finding that the optical purity of the TRANS-isomer 95% e.e. and the CIS isomer 69% e.e.

Experimental example 1

In a 50 ml vessel Slanka, nitrogen purged, 22 mg of 2,2-bis[2-[(4S)-1-naphthylacetic]]propane is added to the white suspension containing 18 mg triftoratsetata copper (I) and 5 ml of dichloroethane, and stirred with a stirrer at room temperature for 10 minutes, getting blue homogeneous solution of the asymmetric complex of copper. Then added to 7.8 g of 2,5-dimethyl-2,4-hexadiene and the internal temperature is brought to 40°C and 1.4 g of tert-butyldiethanolamine is added dropwise within 2 hours and the resulting mixture was stirred at the same temperature for additional 30 minutes to complete the reaction, and tert-butyl-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate get with exit 89% (based on tert-butylcyanoacrylate). The ratio of TRANS-isomer/CIS-isomer = 81/19. Optical net is the TRANS-isomer 86% e.e. and the CIS isomer 60% e.e.

Example 8

23.3 g of 1-Amino-1-(1-naphthyl)-2-methyl-2-propanol is dissolved in 410 ml of isopropanol and the solution is heated to an internal temperature of 60-70°C. a Solution of 8.4 g of N-formyl-L-phenylalanine in 410 ml of isopropanol is added to the resulting solution. The mixture is allowed to stand overnight and the precipitated optically active diastereomer salt of 1-amino-1-(1-naphthyl)-2-methyl-2-propanol and N-formyl-L-phenylalanine are filtering. Filtered diastereomer salt washed with 50 ml of cold isopropanol, getting diastereomer salt. Diastereomer salt again mixed with 750 ml of isopropanol and 40 ml of water and the resulting mixture is heated to boiling point with the return of phlegmy to dissolve diastereomer salt. Then the obtained solution is cooled to room temperature and precipitated diastereomer salt are filtered. Filtered diastereomer salt washed with 50 ml of cold isopropanol, receiving of 14.2 g of white crystalline diastereomeric salt.

Melting point diastereomeric salt 186-188°C. elemental analysis Data: C: 69,8%, H: 7.0% and N: 6,7% (theoretical value : C: 70,6%, H: 6,9%, N: 6.9 per cent).

60 ml of an aqueous solution of 1 mol/l sodium hydroxide, 80 ml of water and 300 ml of chloroform is added to 13.8 g obtained diastereomeric salt. Processing the extraction is carried out at on the th temperature and the organic layer and the aqueous layer was razdelyayut. The obtained organic layer was washed with water and concentrated, obtaining 5.6 g (S)-1-amino-1-(1-naphthyl)-2-methyl-2-propanol (yield: 24%). Optical purity: the ratio of S-isomer = 99.95%

The results of the analysis of (S)-1-amino-1-(1-naphthyl)-2-methyl-2-propanol:

[α] D (c 0.5, CH3OH) +60,4°: melting point 86-87°C:

1H-NMR (300 MHz, CDCl3, TMS standard) range

δ(ppm); of 1.07 (3H, s)of 1.29 (3H, s), 1,50-of 2.16 (2H, W), 2,16-up 3.22 (1H, W), a 4.83 (1H, s), 7,46-8,19 (7H, m).

Elemental analysis data: C: 77.8%, H: 7.9% and N: 6.4% (theoretical value : C: 78.1%, H: 8.0%, N: 6.5%.

Example 9

24,0 g of 1-amino-1-(2-naphthyl)-2-methyl-2-propanol is dissolved in 410 ml of isopropanol and the resulting solution was heated to an internal temperature of 40°C. a Solution of 8.3 g of N-formyl-L-phenylalanine in 410 ml of isopropanol is added to the resulting solution. The mixture is allowed to stand overnight and the precipitated optically active diastereomer salt of 1-amino-1-(2-naphthyl)-2-methyl-2-propanol and N-formyl-L-phenylalanine are filtering. Filtered diastereomer salt washed with 50 ml of cold isopropanol, getting diastereomer salt. Diastereomer salt again mixed with 750 ml of isopropanol and 40 ml of water and the resulting mixture is heated to boiling point with the return of phlegmy to dissolve diastereomer salt. Then the obtained solution is cooled to room temperature and ardanuy diastereomer salt are filtered. Filtered diastereomer salt washed with 50 ml of cold isopropanol, getting 12,4 white crystalline diastereomeric salt.

Melting point diastereomeric salt 193-195°C. elemental analysis Data: C: 70,4%, H: 6.9% and N: 6,8% (theoretical value : C: 70,6%, H: 6,9%, N: 6.9 per cent).

35 ml of aqueous 1 mol/l sodium hydroxide, 100 ml of water and 300 ml of chloroform is added to 11.9 g obtained diastereomeric salt. Processing the extraction was performed at room temperature and the organic layer and the aqueous layer was separated. The obtained organic layer was washed with water and concentrated, obtaining 6.2 g of (S)-1-amino-1-(2-naphthyl)-2-methyl-2-propanol (yield: 26%). Optical purity: the ratio of S-isomer = 99.89 per cent

The results of the analysis of (S)-1-amino-1-(2-naphthyl)-2-methyl-2-propanol:

[α] D (c 0.5, CH3OH) +14,1°: melting point 77-78°C:

1H-NMR (300 MHz, CDCl3, TMS standard) range

δ(ppm); 1,09 (3H, s)of 1.26 (3H, s), 1,47 to 2.35 (2H, W), 2,35-3,20 (1H, W), of 3.97 (1H, s), 7,44-7,83 (7H, m).

Elemental analysis data: C: 78,0%, H: 8.0% N: 6,4% (theoretical value : C: 78,1%, H: 8,0%, N: 6.5 per cent.

Example 10

33 ml of thionyl chloride is added dropwise to the mixture 50,3 g 1-nafcillin (racemic modification) and 200 ml of methanol (digidrirovanny) when the internal temperature of 35°C for 1 hour and the mixture is stirred at the same temperature for 3 hours to implementation is twice reaction. The reaction mixture was concentrated and the concentrated residue is mixed with 200 ml of diethyl simple ether. Then, the resulting crystals are filtered and washed with 50 ml of diethyl simple ether. Crystals, isolated by filtration, dried at an internal temperature of 50°C under reduced pressure, obtaining of 61.9 g of methyl ester hydrochloride 1-nafcillin ochre (yield: 98%).

Then 72 ml of triethylamine is added dropwise to a mixture of 61.9 g the above methyl ester hydrochloride 1-nafcillin and 390 ml of dichloromethane at internal temperatures of -40 to -50°C, to this additionally added dropwise 38 ml triperoxonane anhydride at temperatures from -45 to -50°C for 1 hour. The mixture is additionally stirred at the same temperature for 1 hour to carry out reaction, and then the reaction mixture is allowed to warm to 0°C. a Mixture of 280 ml of cold water and 10 ml of concentrated chloroethanol acids are added to the reaction mixture and processing extraction spend 1100 ml of dichloromethane. The obtained organic layer was washed with 280 ml of cold water. The obtained organic layer is dried over digidrirovanny sodium sulfate and then concentrated, and the precipitated crystals are filtered. After washing with cold dichloromethane crystals are dried at an internal temperature of 6° C under reduced pressure, obtaining of 51.7 g white methyl ester N-(TRIFLUOROACETYL)-1-nafcillin (yield: 68%).

The melting point of methyl ester of N-(TRIFLUOROACETYL)-1-nafcillin: 183-184°C.

1H-NMR (300 MHz, CDCl3, TMS standard) range

δ(ppm); 3,76 (3H, s), of 6.31 (1H, d), 7,30-7,40 (1H, W), 7,46-8,10 (7H, m).

A solution obtained by adding 360 ml of tetrahydrofuran (digidrirovanny) to a solution of bromide Metalmania in 180 ml of tetrahydrofuran (3 mol/l), cooled to an internal temperature of 0-5°C and at this temperature a mixture containing 33,7 g obtained above methyl ester N-(TRIFLUOROACETYL)-1-nafcillin and 170 ml of tetrahydrofuran (digidrirovanny), is added dropwise to this within 30 minutes. The obtained mixture is allowed to warm to room temperature and stirred at the same temperature for 2.5 hours to complete the reaction. The reaction mixture was added to a mixture of 900 g of ice and 200 ml of concentrated chloroethanol acid, maintaining the internal temperature of 5°C or below, and processing extraction spend 800 ml of cold toluene. The resulting aqueous layer is extracted with 800 ml of cold toluene. The obtained organic layer is combined with the previously obtained organic layer and the mixture is washed with 400 ml of cold water. The obtained organic layer is dried over digidrirovanny sulfate on the model and then concentrated, and the concentrated residue is dried at room temperature under reduced pressure, getting 36,0 g blignault viscous and oily 1-(triptorelin)-1-(1-naphthyl)-2-methyl-2-propanol.

1H-NMR (300 MHz, CDCl3, TMS standard) spectrum of 1-(triptorelin)-1-(1-naphthyl)-2-methyl-2-propanol

δ(ppm); and 0.98 (3H, s)of 1.47 (3H, s), of 5.83 (1H, d) 7,46-7,89 (7H, m), 8,18 (1H, d).

180 ml of isopropanol and 180 ml of ethanol is added to 36,0 g of the obtained 1-(triptorelin)-1-(1-naphthyl)-2-methyl-2-propanol and to this is added dropwise 63 g of an aqueous solution of 22% by weight of potassium hydroxide for 30 minutes at room temperature. The internal temperature of the mixture was raised to 50°C and at this temperature the mixture is stirred for 2 hours to carry out reaction. The reaction mixture was concentrated and to the resulting concentrated residue is added 500 ml of chloroform and 180 ml of water, to make the processing of extraction. The obtained organic layer was washed with 100 ml of water and the resulting organic layer is dried over digidrirovanny sodium sulfate and then concentrated. The concentrated residue is dried at an internal temperature of 30°C under reduced pressure, obtaining of 28.0 g of brown viscous and oily 1-amino-1-(1-naphthyl)-2-methyl-2-propanol

1H-NMR (300 MHz, CDCl3, TMS standard) spectrum of 1-amino-1-(1-naphthyl)-2-methyl-2-propanol

δ(ppm); of 1.07 (3H, s)of 1.29 (3H, s), 1,48-to 2.94 (3H, Shir.) a 4.83 (1H, s) 7,46-8,19 (7H, m).

Example 11

33 ml of thionyl chloride is added dropwise to the mixture to 50.3 g of 2-nafcillin (racemic weight) and 200 ml of methanol (digidrirovanny) when the internal temperature of 35°C for 1 hour and the mixture is stirred at the same temperature for 3 hours to carry out reaction. The reaction mixture was concentrated and the concentrated residue is mixed with 200 ml of diethyl simple ether. Then, the resulting crystals are removed by filtration and washed with 50 ml of diethyl simple ether. The crystals are recovered by filtration, dried at an internal temperature of 50°C under reduced pressure, getting 59.0 g of a white hydrochloride methyl ester 2-nafcillin (yield: 94%).

Then a mixture of 59.0 g obtained above methyl ester hydrochloride 2-nafcillin and 1180 ml of dichloromethane is cooled, to the mixture is added dropwise 69 ml of triethylamine at internal temperatures from -35 to -38°C. 38 ml Triperoxonane anhydride addition is added dropwise to this when the internal temperature from -40 to -42°C for 70 minutes. The mixture is additionally stirred with a stirrer at the same temperature for 1 hour to complete the reaction and then the reaction mixture is allowed to warm to 0°C. a Mixture of 280 ml of cold water and 4 ml of concentrated chloroethanol acids are added to the reaction mixture and processing extraction spend 500 is l dichloromethane. The obtained organic layer was washed with 280 ml of cold water. The obtained organic layer is dried over digidrirovanny sodium sulfate and then concentrated, and the precipitated crystals are filtered. After washing with cold mixture of dichloromethane/n-hexane = 1/1 (by volume) crystals are dried at an internal temperature of 60°C under reduced pressure, obtaining of 55.5 g of white methyl ester N-(TRIFLUOROACETYL)-2-nafcillin (yield: 76%).

1H-NMR (300 MHz, CDCl3, TMS standard) spectrum of the methyl ester of N-(TRIFLUOROACETYL)-2-nafcillin

δ(ppm); of 3.77 (3H, s)5,72 (1H, d), 7,41-7,88 (8H, m).

A solution obtained by adding 390 ml of tetrahydrofuran (digidrirovanny) to a solution of bromide Metalmania in 200 ml of tetrahydrofuran (3 mol/l), cooled to an internal temperature of 0 to 5°C and at this temperature a mixture containing 37,0 g obtained above methyl ester N-(TRIFLUOROACETYL)-2-nafcillin and 190 ml of tetrahydrofuran (digidrirovanny), is added dropwise within 30 minutes. The obtained mixture is allowed to warm to room temperature and stirred at the same temperature for 2.5 hours to complete the reaction. Then the reaction mixture was added to a mixture of 900 g of ice and 220 ml of concentrated chloroethanol acid, maintaining the internal temperature of 5°C or below, processing extraction spend 800 ml Kholodnov is toluene. The resulting aqueous layer is extracted with 800 ml of cold toluene. The obtained organic layer is combined with the previously obtained organic layer and washed with 400 ml of cold water. The obtained organic layer is dried over digidrirovanny sodium sulfate and then concentrated. The concentrated residue is dried at an internal temperature of 35°C under reduced pressure, getting 36,0 g blignault solid 1-(triptorelin)-1-(2-naphthyl)-2-methyl-2-propanol.

1H-NMR (300 MHz, CDCl3, TMS standard) spectrum of 1-(triptorelin)-1-(2-naphthyl)-2-methyl-2-propanol

δ(ppm); 1,09 (3H, s)of 1.42 (3H, s), of 4.95 (1H, d) 7,43-a 7.85 (8H, m).

Then 170 ml of isopropanol and 170 ml of ethanol is added to 36,0 g of the obtained 1-(triptorelin)-1-(2-naphthyl)-2-methyl-2-propanol, to this is added dropwise 56 g of an aqueous solution of 22% by weight of potassium hydroxide for 30 minutes at room temperature. Then, the inner temperature of the mixture was raised to 50°C and at this temperature the mixture is stirred for 2 hours to carry out reaction. The reaction mixture was concentrated and 320 ml of chloroform and 160 ml of water is added to the obtained concentrated residue to conduct extraction processing. The obtained organic layer was washed with 80 ml of water and the resulting organic layer is dried over digidrirovanny sodium sulfate and then concentri the comfort. The concentrated residue is dried at an internal temperature of 30°C under reduced pressure, obtaining a 24.3 g of brown solid 1-amino-1-(2-naphthyl)-2-methyl-2-propanol (yield: 97%).

1H-NMR (300 MHz, CDCl3, TMS standard) spectrum of 1-amino-1-(2-naphthyl)-2-methyl-2-propanol

δ(ppm); a 1.08 (3H, s)of 1.26 (3H, s), 1,46 was 3.05 (3H, Shir.) of 3.96 (1H, s) 7,42-7,84 (7H, m).

1. Optically active compound bisoxazoline represented by the formula (1):

where R1and R2are the same and each means C1-6accelgroup, C1-6accelgroup, substituted unsubstituted phenylpropoxy or phenylpropoxy, substituted C1-6the alkyl or C1-6alkoxygroup, the unsubstituted panelgroup, or panelgroup, substituted C1-6the alkyl or C1-6alkoxygroup, or R1and R2together with the carbon atom ring oxazoline to which they are attached, form a ring cycloalkyl having 3-7 carbon atoms; R3means unsubstituted 1-afterglow or 2-aftercrop, or 1-afterglow or 2-aftercrop, substituted with at least one C1-6altergroup or C1-6alkoxygroup; R4and R5are the same and each means a hydrogen atom or a C1-6accelgroup, or R4and R5together with the carbon atom to which they recognize the ENES, form a ring cycloalkyl having 3-6 carbon atoms, and * denotes an asymmetric center.

2. The compound according to claim 1, where R1and R2are the same and each means C1-6altergroup; R3mean 1-afterglow or 2-afterglow; R4and R5are the same and each means a hydrogen atom or a C1-3accelgroup, or R4and R5together with the carbon atom to which they are attached, form a ring cycloalkyl having 3-6 carbon atoms.

3. The compound according to claim 1 or 2, where the configuration of the two asymmetric carbon atoms marked with *are both (S) or (R).

4. A method of obtaining optically active compounds bisoxazoline represented by the formula (1)according to claim 1, including the interaction of the Lewis acid with optically active diamidin compound represented by the formula (2):

where R1and R2are the same and each means C1-6accelgroup, C1-6accelgroup, substituted unsubstituted phenylpropoxy or phenylpropoxy, substituted C1-6the alkyl or C1-6alkoxygroup, or an unsubstituted panelgroup, or panelgroup, substituted C1-6the alkyl or C1-6alkoxygroup, or R1and R2together with the carbon atom to which they are attached, form a ring cycloalkyl having 3-7 carbon atoms; R3means unsubstituted 1-afterglow or 2-aftercrop, or 1-afterglow or 2-aftercrop, substituted with at least one C1-6altergroup or C1-6alkoxygroup; R4and R5are the same and each means a hydrogen atom or a C1-6accelgroup, or R4and R5together with the carbon atom to which they are attached, form a ring cycloalkyl having 3-6 carbon atoms, and * denotes an asymmetric center.

5. The method according to claim 4, where the optically active diamine compound represented by the formula (2)is optically active diamidin compound obtained by the interaction of the optically active amerosport represented by the formula (3):

where R1, R2, R3and * have the meanings specified for formula (2), and compounds of malonic acid represented by the formula (4):

where R4and R5have the meanings specified for formula (2), and Z means alkoxygroup or halogen atom.

6. Optically active diamine compound represented by the formula (2):

where R1and R2are the same and each means C1-6accelgroup, C1-6accelgroup, substituted unsubstituted panelgroup the th or phenylpropoxy, substituted C1-6the alkyl or C1-6alkoxygroup, or an unsubstituted panelgroup, or panelgroup, substituted C1-6the alkyl or C1-6alkoxygroup, or R1and R2together with the carbon atom to which they are attached, form a ring cycloalkyl having 3-7 carbon atoms; R3means unsubstituted 1-afterglow or 2-aftercrop, or 1-afterglow or 2-aftercrop, substituted with at least one C1-6altergroup or C1-6alkoxygroup; R4and R5are the same and each means a hydrogen atom or a C1-6accelgroup, or R4and R5together with the carbon atom to which they are attached, form a ring cycloalkyl having 3-6 carbon atoms, and * denotes an asymmetric center.

7. A method of obtaining optically active dumenigo compounds represented by formula (2):

where R1and R2are the same and each means C1-6accelgroup, C1-6accelgroup, substituted unsubstituted phenylpropoxy or phenylpropoxy, substituted C1-6the alkyl or C1-6alkoxygroup, the unsubstituted panelgroup, or panelgroup, substituted C1-6the alkyl or C1-6alkoxygroup, or R1and R2together with the carbon atom ring oxazoline to which they p is soedinenii, form a ring cycloalkyl having 3-7 carbon atoms; R3means unsubstituted 1-afterglow or 2-aftercrop, or 1-afterglow or 2-aftercrop, substituted with at least one C1-6altergroup or C1-6alkoxygroup; R4and R5are the same and each means a hydrogen atom or a C1-6accelgroup, or R4and R5together with the carbon atom to which they are attached, form a ring cycloalkyl having 3-6 carbon atoms, and * denotes an asymmetric center, including the interaction of optically active amerosport represented by the formula (3):

where R1, R2, R3and * have the meanings specified for formula (2), with the compound of malonic acid represented by the formula (4):

where R4and R5have the meanings specified for formula (2), and Z means alkoxygroup or halogen atom.

8. Asymmetric copper complex obtained from copper compounds and optically active compounds of bisoxazoline represented by the formula (1):

where R1and R2are odinakovimi and every means C1-6accelgroup, C1-6accelgroup, substituted unsubstituted phenylpropoxy or phenylpropoxy, C is displaced C 1-6the alkyl or C1-6alkoxygroup, the unsubstituted panelgroup, or panelgroup, substituted C1-6the alkyl or C1-6alkoxygroup, or R1and R2together with the carbon atom ring oxazoline to which they are attached, form a ring cycloalkyl having 3-7 carbon atoms; R3means unsubstituted 1-afterglow or 2-aftercrop, or 1-afterglow or 2-aftercrop, substituted with at least one C1-6altergroup or C1-6alkoxygroup; R4and R5are the same and each means a hydrogen atom or a C1-6accelgroup, or R4and R5together with the carbon atom to which they are attached, form a ring cycloalkyl having 3-6 carbon atoms, and * denotes an asymmetric center.

9. Asymmetric copper complex of claim 8, where R1and R2are the same and each means C1-6altergroup; R3mean 1-afterglow or 2-afterglow; R4and R5are the same and each means a hydrogen atom or a C1-3accelgroup, or R4and R5together with the carbon atom to which they are attached, form a ring cycloalkyl having 3-6 carbon atoms.

10. Asymmetric copper complex of claim 8, where the configuration of the two asymmetric carbon atoms marked with *are both (S) or (R).

11. Pic is b obtain optically active compounds of cyclopropane, represented by the formula (7):

where R6, R7, R8and R9are the same or different and independently denote a hydrogen atom, accelgroup, optionally substituted by a halogen atom, altergroup, optionally substituted by a halogen atom, a substituted or unsubstituted aryl or arakalgudu, provided that when R6and R8are the same, R6and R7are different from each other; and R10means C1-6accelgroup, including interaction prehiring of olefin represented by the formula (5):

where R6, R7, R8and R9have the above values, with complex air diazo acetic acid represented by formula (6):

where R10matter mentioned above, in the presence of an asymmetric complex of copper on p, 9, or 10.

12. Optically active amerosport represented by the formula (30):

where R31, R32, R33and R34are the same or different and independently denote a hydrogen atom, a C1-6altergroup or C1-6alkoxygroup; R35means C1-6accelgroup, the unsubstituted panelgroup or panelgroup substituted C 1-6the alkyl or C1-6alkoxygroup, or C1-6accelgroup, substituted unsubstituted phenylpropoxy or phenylpropoxy, substituted C1-6the alkyl or C1-6alkoxygroup, or two R35related to the same carbon atom, together with this carbon atom form a ring cycloalkyl having 3-7 carbon atoms; and * indicates an asymmetric carbon atom.

13. A method of obtaining optically active neftianogo alcohol, including the interaction of amerosport represented by the formula (40):

where R31, R32, R33and R34are the same or different and independently denote a hydrogen atom, a C1-6altergroup or C1-6alkoxygroup; R35means C1-6accelgroup, the unsubstituted panelgroup or panelgroup, substituted C1-6the alkyl or C1-6alkoxygroup, or C1-6accelgroup, substituted unsubstituted phenylpropoxy or phenylpropoxy, substituted C1-6the alkyl or C1-6alkoxygroup, or two R35related to the same carbon atom, together with this carbon atom form a ring cycloalkyl having 3-7 carbon atoms with optically active N-formylphenylboronic in the solvent with the formation of the diastereomeric salt of optically active naftalovich alcohols and optically active is th N-formylphenylboronic, represented by the formula (30):

where R31, R32, R33, R34and R35have the above values and * denotes an asymmetric carbon atom, the separation of one diastereomeric salt from another diastereomeric salt and then processing the separated diastereomeric alkali salt.

14. Diastereomer salt of optically active amerosport represented by the formula (30):

where R31, R32, R33and R34are the same or different and independently denote a hydrogen atom, a C1-6altergroup or C1-6alkoxygroup; R35means C1-6accelgroup, the unsubstituted panelgroup or panelgroup, substituted C1-6the alkyl or C1-6alkoxygroup, or C1-6accelgroup, substituted unsubstituted phenylpropoxy or phenylpropoxy, substituted C1-6the alkyl or C1-6alkoxygroup, or two R35related to the same carbon atom, together with this carbon atom form a ring cycloalkyl having 3-7 carbon atoms, and * indicates an asymmetric carbon atom, and optically active N-formylphenylboronic.

15. The method of producing amerosport represented by the formula (40):

where R31, R32, R33The R 34are the same or different and independently denote a hydrogen atom, a C1-6altergroup or C1-6alkoxygroup, R35means C1-6accelgroup, the unsubstituted panelgroup or panelgroup, substituted C1-6the alkyl or C1-6alkoxygroup, or C1-6accelgroup, substituted unsubstituted phenylpropoxy or phenylpropoxy, substituted C1-6the alkyl or C1-6alkoxygroup, or two R35related to the same carbon atom, together with this carbon atom form a ring cycloalkyl having 3-7 carbon atoms, comprising the following stages (A)to(D):

(A) the interaction of compounds nafcillin represented by the formula (41):

where R31, R32, R33and R34are odinakovimi or different and independently denote a hydrogen atom, a C1-6altergroup or C1-6alkoxygroup, with a chlorination agent and the alcohol represented by the formula (42):

where R9means C1-6accelgroup, to obtain the hydrochloride of ester of the amino acids represented by the formula (43):

where R31, R32, R33, R34and R9have the above values,

(B) interaction hydrochloride is a complex ester of the amino acids, represented by the formula (43), obtained at this stage (A), with the compound represented by the formula (44);

where n is 1, 2 or 3, or formula (45):

where n has the above meanings, and X is a chlorine atom, bromine atom or iodine atom, in the presence of a tertiary amine, to obtain the compound represented by the formula (46):

where R31, R32, R33, R34, R9and n have the above values,

(C) interaction of the compound (46)obtained at this stage (In), with the compound represented by the formula (47):

where R35means C1-6accelgroup, C1-6accelgroup, substituted unsubstituted phenylpropoxy or phenylpropoxy, substituted C1-6the alkyl or C1-6alkoxygroup, the unsubstituted panelgroup or panelgroup, substituted C1-6the alkyl or C1-6alkoxygroup, and X' denotes a halogen atom, or a compound represented by the formula (48):

where R35'means2-6akilagpa and X' have the values specified above, to obtain compounds represented by formula (49):

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where R31, R32, R33, R34, R35and n have the above values, and

(D) interaction of the compound (49)obtained at the specified stage (s)at the base.

16. The compound represented by formula (49):

where R31, R32, R33and R34are the same or different and independently denote a hydrogen atom, a C1-6altergroup or C1-6alkoxygroup; R35means C1-6accelgroup, the unsubstituted panelgroup or panelgroup, substituted C1-6the alkyl or C1-6alkoxygroup, or C1-6accelgroup, substituted unsubstituted phenylpropoxy or phenylpropoxy, substituted C1-6the alkyl or C1-6alkoxygroup, or two R35related to the same carbon atom, together with this carbon atom form a ring cycloalkyl having 3-7 carbon atoms; n is 1, 2 or 3.

Priority items:

07.02.2003 according to claims 1-16;

16.05.2003 according to claims 1-16.



 

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10 cl, 1 tbl, 13 ex

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