Optically-active-aminoalkoxide complex method thereof, optically active-aminopyrrolo derived to obtain and methods for producing optically active alcohols involving complex

 

(57) Abstract:

The proposed optically active-aminoalkoxide complex of formula (1), where R1- C1-C8alkyl or C7-C11aralkyl, R2- C1-C8alkyl, C3-C7cycloalkyl or C7-C11aralkyl, or R1and R2together form a (CH2)nwhere n is 3 or 4, and Ar is naphthyl, antrel or tenantry, which may be substituted by 1 to 3 substituents selected from the group comprising halogen, C1-C6alkyl, C6-C10aryl and C1-C6alkoxy, and optically active-aminopyrene derivative of the formula (II), where R1- C1-C8alkyl or C7-C11aralkyl, R2- C1-C3alkyl, C3-C7cycloalkyl or C7-C11aralkyl, or R1and R2together form a (CH2)nwhere n is 3 or 4, and Ar is naphthyl, antrel or tenantry, which may be substituted by 1 to 3 substituents selected from the group comprising halogen, C1-C6alkyl, C6-C10aryl and C1-C6alkoxy, provided that when Ar is naphthyl, R2is not C1-C alkyl, or, when AG - phenanthrol, R1and R2do not form the present invention provide a higher level of asymmetric and high diastereoselectivity (higher degree of SYN-education), than the standard catalysts boranova complex. The proposed compounds may find application in pharmaceuticals, agriculture, or for cosmetic purposes.

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7 c.p. f-crystals, 6 PL.

The present invention relates to new optically active-aminoalkoxide complex and to a method for producing optically active alcohol using the complex as a reducing agent. In particular, the invention relates to a method for producing optically active 1,3-SYN-delovogo connection with the use of this boranova complex for the recovery of 1,3-dicarbonyl compounds.

Many physiologically active substances for use in pharmaceuticals, agriculture, or for cosmetic purposes, has a 1,2 - or 1,3-SYN-volovoy structure. For example, a number of inhibitors inhibitors of coenzyme A (HMG-CoA), which is one of the classes antihyperlipidemic agents have in their melanocortin parts, as a common structural element, 1,3-min-diol, which is the main structure responsible for reductonebria activity.

Among the natural physiologically active Veselaya activity promote generic activities or Sadashiva activity; pentamycin representing a polyene macrolide antibiotic; amphotericin b, which represents a polyene antifungal agent; misfired And representing antitumor macrolide; G-strophanthin, representing a cardiac glycoside; and Pulgarin representing sesquiterpenes, which is contained in Giardia beautiful (Gaillardia pulchella) (an ornamental plant).

Currently, different methods of obtaining the above 1,3-SYN-diols (Tetrahedron Lett. , 28, 155 (1987), Tetrahedron Lett., 26, 2951 (1985)). However, since these compounds enter the first chiral center and on the basis of this first chiral center is formed a second chiral center, all of these methods must be multi-stage and for the reaction to obtain the desired 1,3-SYN-diol with high optical output and high SYN-selectivity requires extremely low temperatures. Therefore, these methods have many limitations for industrial use.

In addition, currently there are a large number of methods for obtaining optically active alcohol by asymmetric in the are, for example, the method of Corey and others (E. J. Corey & A. V. Gavai, Tetrahedron Lett., 29, 3201 (1988)), involving the use of optically active boranova complex; asymmetric method recovery Meerwein-Ponndorf-Verley (MPV) (M. M. Midland, D. C. McDowell & Gabriel, J. Org. Chem. , 54, 154 (1989)); and the method involving the use of an enzyme or microorganism (G. Frater, Helv. Cgim.Acta, 62, 2815, 2829 (1979)). To implement asymmetric recovery of aromatic carbonyl compounds was developed many chemical agents with high selectivity. However, points to the difficulty of achieving high selectivity in asymmetric restoring dialkylammonium, even with the use of these reagents, and in the best case, the output of the asymmetric product is achieved only 50%. It is believed that when asymmetric restoring a high concentration of electrons from unsaturated groups of aromatic carbonyl compounds has a significant impact on the transition state, and for dicarbonyl, one cannot expect such a significant electronic effects, a necessary reagent having the ability to recognize differences in steric effects (Organic Synthetic Chemistry, vol. 45, N 2, p. 101 (1987)). Accordingly, in the case of such a substrate as 2-gäutan. The above reagents for asymmetric restore all used only for asymmetric recovery monocarbonyl compounds; and only in the few cases known to the application of these reagents to restore dicarbonyl compounds.

On the other hand, the known method (Yamazaki and others), which uses an optically active bananowy complex (Japanese publication of unexamined application N 146786/1982). This method, in particular, relates to asymmetric recovery acetophenone using optically active boranova complex derived from (S)-1-benzyl-2-pyrrolidineethanol and borane. However, the maximum optical purity that can be achieved is only 69%, and the reaction time is about 60 hours. Therefore, the above method can hardly be used in practice. Itsuno and others tried to asymmetric reduction of carbonyl compounds using boranova complex containing styrene polymer, introduced in benzyl radical (S)-1-benzyl-2-pyrrolidineethanol (S. Itsuno, K. Ito, T. Maruyama, A. Hirao & S. Nakahama, Bul. Chem. Soc. Jpn. , 59:3329 (1986)); however, these attempts failed because sufficient degree historyonline compounds and were not used for recovery dicarbonyl compounds. To restore dicarbonyl compounds method was developed by Noyori et al. Ryoji Noyori & Hidemasa Takaya, Chemistr, 43, 146 (1988) and R. Noyori, Chem.Soc.Rev., 18, 187 (1988)), uses BINAP-Ru complex; moreover, this method was also used for direct reduction of 1,2-dicarbonyl and 1,3-dicarbonyl compounds. However, in any case, the obtained optically active diols represented anisometry.

Method, recently developed Hiyama, etc. for direct asymmetric recovery of 1,3-dicarbonyl compounds containing typed them in asymmetric ester groups (Europatent N 475627), or method of asymmetric recovery of 1,3-dicarbonyl compounds with an optically active boranova reagent (Tetrahedron Lett., 29, 6467 (1988)), were obtained 1,3-SYN-dialogue connection through the proposed SYN-selective asymmetric recovery, however, adequate results in asymmetric release was not obtained. Thus, the method of direct reduction of carbonyl compounds with obtaining optically active SYN-dolovich compounds has not yet been developed.

The essence of the invention.

The object of the present invention is the floor of the carbonyl compounds; in particular, obtaining optically active 1,3-SYN-delovogo connection with good asymmetric yield and with a high degree of SYN-education simultaneous recovery of two carbonyl groups dicarbonyl compounds; as well as a highly efficient catalyst recovery for the synthesis of optically active 1,3-SYN-delovogo connection.

The authors of the present invention have conducted extensive studies in order to develop remediation reagent to achieve high output asymmetric product with high SYN-selectivity and used in a wide range of reaction conditions, and develop a method of producing optically active 1,3-SYN-delovogo connection, resulting in it was found that the optically active 1,3-SYN-dialogue connection can be obtained with maximum asymmetric output, constituting 100%, with high SYN-selectivity component of the 99% by the recovery of 1,3-dicarbonyl compounds with an optically active -(N-naphthylmethyl)aminoalkoxide complex derived from optically active -(N-naphthylmethyl)amerosport and borane. The results of these studies were the basis of the us is alkoxygroup complex of formula I:

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where R1is Wal1- C8-alkyl or C7- C11-aralkyl, R2represents a C1- C8-alkyl, C3- C7-cycloalkyl or7- C11-aralkyl, or R1and R2together form a (CH2)nwhere n is 3 or 4, and Ar represents naphthyl, antrel or tenantry, which may be substituted by 1 to 3 substituents selected from the group comprising halogen, C1- C6-alkyl, C6- C10-aryl and C1- C6-alkoxy.

In addition, the present invention relates to optically active-aminopyrene derivative of the formula (II)

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where R1represents a C1- C8-alkyl or C7- C11-aralkyl, R2represents a C1- C8-alkyl, C3- C7-cycloalkyl or7- C11-aralkyl, or R1and R2together form a (CH2)nwhere n is 3 or 4, and Ar represents naphthyl, antrel or tenantry, which may be substituted by 1 to 3 substituents selected from the group comprising halogen, C1- C6-alkyl, C6- C10-aryl and C1- C6-alkoxy, provided that when Ar represents naphthyl, R22)3.

The invention relates also to a method for producing optically active-aminoethoxy-Baranovka complex of formula (I), above, which lies in the interaction of optically active-aminopyrrolo derivative of the formula (IX):

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where R1represents a C1- C8-alkyl or C7- C11-aralkyl, R2represents a C1- C8-alkyl, C3- C7-cycloalkyl or7- C11-aralkyl, or R1and R2together form a (CH2)nwhere n is 3 or 4, and Ar represents naphthyl, antrel or tenantry, which may be substituted by 1 to 3 substituents selected from the group comprising halogen, C1- C6-alkyl, C6- C10-aryl and C1- C6-alkoxy, boranova reagent, such as selected from the group including, for example, a complex of borane-tetrahydrofuran, borane complex-diethyl ether complex, borane-pyridine complex borane-ammonia complex, borane-tert-butylamine, complex, borane-N, -N-diethylaniline, complex, borane-N, N-diisopropylethylamine, complex, borane-dimethylamine complex borane-4-dimethylaminopyridine, complex, borane-4-ethylmorpholine, complex bromethalin, sets the e the invention relates to a method for producing optically active alcohol compounds of formula (IV):

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where R3and R4differ from each other and represent a1- C10-alkyl, C2- C10alkenyl,2- C10-quinil,6- C14-aryl, or R3and R4together form a 5 - to 6-membered cycle, which is condensed with benzene ring, * indicates an optically active center, by stereoselective recovery carbonyl derivative of the formula (III):

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where R3and R4defined above,

optically active-aminoalkoxide complex, obdelennymi above.

In addition, the present invention relates to a method for obtaining compounds of formula (VI-I):

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where R6represents a C1- C10-alkoxy, R7represents a C1- C7-alkyl or C3- C7-cycloalkyl, R8denotes phenyl which may be substituted by fluorine, chlorine or bromine, and indicates an optically active center, provided that the two optically active centre take inconformity in relation to each other, namely, that restores the 1,3-dicarbonyl compound of the formula (V-I):

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where R6, R7and R8defined above, optically active-aminoanthracene optically active 1,3-SYN-delovogo the compounds of formula (VI-2):

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where R5represents hydrogen, R6represents a C1- C10-alkoxy, and * indicates an optically active center, provided that the two optically active centre take inconformity in relation to each other, namely, that restores the 1,3-dicarbonyl compound of the formula (V-2):

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where R5and R6defined above, optically active-aminoalkoxide complex defined above.

In the present description n means normal, i is ISO, sec - secondary, t (t) - tertiary, Me is methyl, Et is ethyl, Bu is butyl, Ph is phenyl, and THF is tetrahydrofuran.

Description of the preferred variants of the invention

Below is a detailed description of the compounds of the present invention. As substituents for R1in each of formulas (I) and (II) you can specify the following substituents: WITH1- C8-alkyl includes, for example, methyl, ethyl, n-propyl, ISO-propyl, n-butyl, ISO-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl and n-octyl.

WITH3- C7-cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

WITH7- C11-aralkyl includes ITIL, m-methylphenyl, p-methylphenyl, 3-phenylpropyl, 3-(o-were)propyl, 3-(m-were)propyl, 3(p-were)propyl, 4-phenylbutyl-naphthylmethyl and-naphthylmethyl.

WITH6- C10aryl includes, for example, phenyl, o-tolyl, m-tolyl, p-tolyl, 2,3-dimetilfenil, 2,4-dimetilfenil, 2,5-dimetilfenil, 2,6-dimetilfenil, 3,4-dimetilfenil, 3, 5dimethylphenyl, 2,3,4-trimetilfenil, 2,3,5-trimetilfenil, 2,3,6-trimetilfenil, 3,4,5-trimetilfenil, 3,4,6-trimetilfenil, 2,4,6-trimetilfenil, -naphthyl and naphthyl.

WITH1- C8-alkyl, C3- C7-cycloalkyl and C7- C11-aralkyl as substituents for R2are the same as the corresponding substituents for R1.

Ar represents naphthyl, antrel or fematril, which may not necessarily be substituted by 1 to 3 substituents selected from the group comprising halogen, nitro, C1- C6-alkyl, C3- C7-cycloalkyl,2- C6alkenyl,2- C6-quinil,7- C11-aralkyl,6- C10-aryl, C1- C6-alkoxy and styrene polymer substituents. Representatives of the substituents will be described next.

The halogen includes fluorine, chlorine, bromine and iodine.

WITH3- C7-cycloalkyl is the same as the corresponding Deputy for R1.

WITH2- C6alkenyl includes, for example, vinyl, 2-propenyl, 3-butenyl, 4-pentenyl and 5-hexenyl.

WITH2- C6-quinil includes, for example, ethinyl, 2-PROPYNYL, 3-butynyl, 4-pentenyl and 5-hexenyl.

WITH1- C6-alkoxy includes, for example, methoxy, ethoxy, n-propoxy, propoxy, n-butoxy, out-butoxy, sec-butoxy, tert-butoxy, n-pentox and n-hexose.

The compounds of formula (I) and (II) of the present invention include compounds shown in table. 1. It should be noted that the compounds of the present invention is not limited to such specific examples. In table. 1 IU is a methyl group; t-Bu represents a tertiary boutelou group and Ph represents a phenyl group.

Below describes in detail the synthesis boranova complex (I) and asymmetric reduction of carbonyl compounds using boranova complex.

In accordance with the present invention, optically active derivative of amerosport (II) and boranova complex (I) can be formed and active-amerosport formula (VIII), which, in turn, can be easily obtained from a complex ester of the amino acid in accordance with known methods (JIKKEN CALLED KOZA 17, YUKI KAGOBUTSU NO HANNO (GE) p. 25, P. Karrer, P. Portmann & Suter, Helv. Cgim. Acta, 31, 1617 (1948); P. Karrer & P. Portmann, see above, 32, 1034 (1949); P. Karrer, P. Portmann & M. Suter, see above, 32, 1156 (1949); R. R. Gebhard & P. Karrer, see above, 38, 915 (1955); Synthetic Methods of Organic Chemistry Vol. 11, 52; H. Bauer, E. Adams & H. Tabor, Biochem, Prep. 4, 46 (1955)).

In the reaction scheme below is a method for the synthesis of optically active-aminoalkoxide complex of formula (I) and optically active-amerosport formula (II). In these formulas, R1, R2and Ar are as defined above.

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Stage And represents the reduction of the ester moiety of the ester of the amino acid (VII) with the formation of the alcohol (VIII). As a reducing agent can be used, for example, lithium-aluminiumhydride, diisobutylaluminium, diaconiology sodium or literalized. Preferred is the use of sociallyengaged. As solvent in the reaction may be used a solvent of the ether type, such as diethyl ether, di-n-propyl ether, tetrahydrofuran, 1,3 - or 1,4-dioxane. It is preferable to use the 60oC, preferably from -10oC to 20oC.

Stage is reaction formation oxazolidinone ring by condensation with dehydration of amerosport (VIII) obtained in stage A, with an aromatic aldehyde. The solvent in the reaction can be, for example, an alcohol solvent such as methanol, ethanol, n-propanol, polar solvent, such as acetonitrile, dimethylformamide or dimethyl sulfoxide, a solvent halogen type, such as dichloromethane, 1,1 - or 1,2-dichloroethane, chloroform or Tetrachloromethane, or an ethereal solvent such as diethyl ether, di-n-propyl ether, tetrahydrofuran, 1,3 - or 1,4-dioxane. Preferably the user is methanol, acetonitrile or tetrahydrofuran. The reaction can be conducted at a temperature of from -78oWith up to 60oC, preferably from -10o30oC.

Stage C is the reaction obtain the N-(aryl)methyl-amerosport (II) by reductive opening of the ring oxazolidinone compound (IX) obtained in stage C. as a reducing agent can be used, for example, sociallyengaged, diisobutylaluminium, diaconiology sodium borohydride lithium borohydride or potassium borohydride spirtovoi solvent, such as methanol, ethanol, n-propanol or ISO-propanol, or an ether solvent such as diethyl ether, di-n-propyl ether, tetrahydrofuran, 1,3 - or 1,4-dioxane. Preferably used is methanol, ethanol or tetrahydrofuran. The reaction can be conducted at a temperature of from -78oC to 60oC, preferably from -10o20oC.

Stage D is another way of synthesis derived B-(aryl)methyl-amerosport (II). That is, the derived N-(aryl) methyl-amerosport (II) is produced by interaction of amerosport (VIII) with an appropriate allotropy ether sulfonic acid.

As sulfonate having arylmethyl group, can be used, for example, mesilate, bansilalpet, p-chlorobenzenesulfonate, p-toluensulfonate, p-nitrobenzenesulfonate or trifluromethanesulfonate. Preferably used mesilate. As a base may be used or unsaturated tertiary amine, such as triethylamine, trimethylamine, pyridine, DBU (1,8-diazabicyclo[5.4.0] -7-undecene) or DBN (1,5-diazabicyclo [4.3.0] -5-nonen). Preferably used is triethylamine. The solvent in the reaction can be, for example, ether solvent such as diethyl ether, di-n-propylaminosulfonyl, or a halogen solvent type, such as dichloromethane, 1,1 - or 1,2-dichloroethane, chloroform or Tetrachloromethane. Preferably used is dichloromethane or chloroform, more preferably dichloromethane. This reaction can be conducted at a temperature of from -78oC to 60oC, preferably from -10o30oC.

Stage E is the reaction of synthesis aminoalkoxide complex (I) by reacting N-(aryl)methyl-amerosport (II) obtained in stage C or D with boranova reagent. As boranova reagent can be used, for example, complex balancetransfer, complex brandimay ether complex branfireun, complex branaman, complex brandreth-butylamine complex N,N-diethylaniline, complex N,N-diisopropylethylamine, complex berendililerin, complex boron-dimethylaminopyridine, complex boron-ethylmorpholine, complex parentrelations, complex borontrifluoride or complex of triphenyl borane. Preferably use complex balancetransfer or bordetellosis ether. It is preferable to use complex balancetransfer. The solvent may be, for example, an alcohol, such as methane is ethylsulfonyl, the solvent halogen type, such as dichloromethane, 1,1 - or 1,2-dichloroethane, chloroform or Tetrachloromethane, or an ethereal solvent such as diethyl ether, di-n-propyl ether, tetrahydrofuran, 1,3 - or 1,4-dioxane. It is preferable to use methanol, dichloromethane, diethyl ether or tetrahydrofuran. More preferably tetrahydrofuran. The reaction can be conducted at a temperature of about -100oup to 80oC, preferably at a temperature of from -78o40oC.

-Aminoalkoxide complex (I) is resistant to light, heat and water, and is soluble in various solvents, which makes it very convenient to use in experiments.

In addition, in some cases, aminoalkoxide complex (I) can be formed in the reaction system when adding a derived N-(aryl)methyl-amerosport (II) and boranova reagent in the process of recovery of carbonyl compounds, without highlighting.

Carbonyl compound of the formula (III) or (V) is subjected to reaction stereoselective recovery using an optically active -/ aminoalkoxide complex (I) recip
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Appropriate substituents in the compounds of formula (III), (IV), (V) and (VI) described below.

R3and R4differ from each other and represent a1- C10-alkyl, C3- C10-cycloalkyl,2- C10alkenyl,2- C10-quinil,3- C10-cycloalkenyl,7- C11-aralkyl or6- C14-aryl. On the other hand, R3and R4taken together, may form a cyclic structure.

WITH1- C10-Alkyl includes, for example, methyl, ethyl, n-propyl, ISO-propyl, n-butyl, ISO-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl and n-decanol.

WITH3- C10-Cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cycloneii and cyclodecane.

WITH2- C10Alkenyl includes, for example, vinyl, 1-propenyl, 1-methylethenyl, 2-propenyl, 1,2-dimethyl-1-propenyl, 1-butenyl, 1-pentenyl, 1-hexenyl, 1-heptenyl, 1-octenyl, 1 nonanal and 1-decenyl.

WITH2- C10-Quinil includes, for example, ethinyl, 1-PROPYNYL, 2-PROPYNYL, 1-butynyl, 3-methyl-1-butynyl, 1-pentenyl, 1-hexenyl, 1-heptenyl, 1-octenyl, 1-nonyl, 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl and 3-cyclohexenyl.

WITH7- C11-Aralkyl is the same as the corresponding substituents for R1.

WITH6- C14Aryl includes, for example, phenyl, o-tolyl, m-tolyl, p-tolyl, 2,3-dimetilfenil, 2,4-dimetilfenil, 2.5-dimethylphenyl, 2,6-dimetilfenil, 3,4-dimetilfenil, 3, 5dimethylphenyl, 2,3,4-trimetilfenil, 3,4,6-trimetilfenil, 2,4,6-trimetilfenil, 2-course, 3-course, 4-course, 3,4-dichlorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-acid, 3-nitrophenyl, naphthyl, naphthyl, (2-methyl)-2-naphthyl, (3-methyl)-1-naphthyl, (4-methyl)-1-naphthyl, (5-methyl)-1-naphthyl, (6-methyl)-1-naphthyl, (7-methyl)-1-naphthyl, (8-methyl)-1-naphthyl, (1-methyl)-2-naphthyl, (3-methyl)-2-naphthyl, (4-methyl)-2-naphthyl, (5-methyl-2-naphthyl, (6-methyl)-2-naphthyl, (7-methyl)-2-naphthyl, (8-methyl)-2-naphthyl, (2-ethyl)-1-naphthyl, (3-ethyl)-1-naphthyl, (4-ethyl)-1-Patil, (5-ethyl)-1-naphthyl, (6-ethyl)-1-naphthyl, (7-ethyl)-1-naphthyl, (8-ethyl)-1-naphthyl, (1-ethyl)-2-naphthyl, (3-ethyl)-2-naphthyl, (4-ethyl)-2-naphthyl, (5-ethyl)-2-naphthyl, (6-ethyl)-2-naphthyl, (7-ethyl)-2-naphthyl, (8-ethyl)-2-naphthyl, (2-propyl)-1-naphthyl, (3-propyl)-1-naphthyl, (4-propyl)-1-naphthyl, (5-propyl)-1-naphthyl, (6-propyl)-1-naphthyl), (7-propyl)-1-naphthyl, (8-propyl)-1-naphthyl, (1-propyl)-2-naphthyl, (3-propyl)-2-naphthyl, (4-propyl)-2-naftel, 3-phenanthrol, 4-phenanthrol and 9-phenanthrol.

The cyclic structure of education R3and R4taken together, include, for example, 1-methylcyclobutane, 2,2-dimethylcyclobutane, 2,2-diethyltoluene, 2,2-di-n-propylcyclohexane, 2,2-di-ISO-propylcyclohexane, 2,2-di-n-butylcyclohexane, 2,2-di-ISO-butylcyclohexanone, 2,2-di-sec-butylcyclohexanone, 2,2-di-tert-butylcyclohexanone, 2,2-di-n-pentylcyclohexane, 2,2-di-n-hexylsilane, 1-methylcyclopentanol, 2,2-dimethylcyclopentane, 2,2-diethylstilbestrol, 2,2-di-n-propylcyclohexane, 2,2-di-ISO-propylcyclohexane, 2,2-di-n-butylcyclopentadienyl, 2,2-di-ISO-butylcyclopentadienyl, 2,2-di-sec-butylcyclohexanone, 2,2-di-tert-butylcyclohexanone, 2,2-di-n-pentylcyclohexane, 2,2-di-n-hexylthiophene, trimethylcyclohexane, 2,2-dimethylcyclohexanone, 2,2-diethylsiloxane, 2,2-di-n-propylcyclohexane, 2,2-di-ISO-propylcyclohexane, 2,2-di-n-butylcyclohexane, 2,2-di-ISO-butylcyclohexanone, 2,2-di-sec-butylcyclohexanone, 2,2-di-tert-butylcyclohexanone, 2,2-di-n-pentylcyclohexane, 2,2-di-n-sexycollegegirl, CYCLOBUTANE, 2-cyclopentenone, 2-cyclohexenone, 2-indanone and 1-tetralone.

X represents Suzi, -CH2-, -CH2CH2-, -CH=CH-, -(CH3)=CH-,UP>10
) (where each of R9and R10independently represents hydrogen or C1- C3-alkyl, or R9and R10taken together, form WITH the2- C5-alkylen), CH2OR11(where R11represents hydrogen, C1- C3-alkyl, benzyl which can be substituted by stands or methoxy group, trityl, tetrahydropyranyl, methoxymethyl, trimethylsilyl, dimethyl-tert-Boticelli or diphenyl-tert-butisol), CH2R12( where R12is fluorine, chlorine, bromine or iodine), CN, CO2R13( where R13represents hydrogen, C1- C4-alkyl or benzyl, which can be replaced by stands or methoxy), CONR14R15(where each of R14and R15independently we see hydrogen, C1- C3-alkyl, benzyl, 1-methylbenzyl or phenyl which can be substituted by stands or methoxy).

Each of R9and R10independently represents hydrogen, methyl, ethyl, n-propyl or ISO-propyl, or R9and R10taken together, may form ethylene, trimethylene or 2,2-dimethyl-1,3-trimethylene.

R11can represent hydrogen, methyl, ethyl, n-propyl, ISO-propyl, o-methylbenzyl, m-oximeter, trimethylsilyl, dimethyl-tert-Boticelli or diphenyl-tert-Boticelli.

R12is fluorine, chlorine, bromine or iodine.

R13can represent hydrogen, methyl, ethyl, n-propyl, ISO-propyl, n-butyl, ISO-butyl, tert-butyl, o-methylbenzyl, m-methylbenzyl, p-methylbenzyl, o-methoxybenzyl, m-methoxybenzyl or p-methoxybenzyl.

Each of R14and R15independently can represent hydrogen, methyl, ethyl, n-propyl, ISO-propyl, benzyl, 1-methylbenzyl, were, m-were p-were, o-methoxyphenyl, m-methoxyphenyl or p-methoxyphenyl.

When X is-CH2-, CH2CH2-, -CH=CH-, -(CH3)=CH-, -CH=C(CH3)- or-S-, R5represents hydrogen, trialkylsilyl, aliphatic ring group, aromatic ring group, heterocyclic aromatic group, a condensed heterocyclic aromatic group, an unsaturated aliphatic group or a cyclic unsaturated aliphatic group.

Trialkylsilyl includes, for example, trimethylsilyl, triethylsilyl, tri-n-propulsion, tri-ISO-propulsion, tri-n-Boticelli, tri-ISO-Boticelli, tri-n-exelsior, dimethylethylene, dimiti the dimethyl-n-octylsilane, dimethylcyclohexylamine, dimethylhexylamine, dimethyl-2,3-dimethylpropylene, dimethyl-2-(bicycloheptene)silyl, dimethylbenzidine, dimethylaniline, dimethyl-p-tailcall, dimethyltrimethylene, methyldiphenylamine, triphenylsilane, diphenyl-tert-Boticelli, tribenzylamine, diphenylvinylene, diphenyl-n-butalbitol and phenylmethylsulfonyl.

Aliphatic ring group may be, for example, hexahydronaphthalen or tetrahydronaphthyl, which can be substituted by one or more substituents selected from R7C2- C6-acyloxy and hydroxy, and preferably is a group:

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The aromatic ring group may be, for example, phenyl or naphthyl which may be substituted by 1 to 3 substituents selected from R7and/or 1 to 2 substituents selected from R8and preferably is a group:

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Heterocyclic aromatic group may be, for example, pyridyl, pyrimidinyl, pyrazolyl, imidazolyl, pyrrolyl, thienyl or furanyl, which may be substituted by 1 to 3 substituents selected from R7WITH1- C3-alkoxymethyl, phenylcarbamoyl, and/or 1 or 2 substituents selected from R8and prepacker, indolyl, hinely, pyrazolidine, cyanopyridyl, pyrrolopyridine or athinaikon, which may be substituted by 1 to 3 substituents selected from R7WITH1- C3-alkoxymethyl, phenylcarbamoyl, and/or 1 or 2 substituents selected from R8and preferably is a group:

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Unsaturated aliphatic group may be, for example, ethynyl or ethinyl, which can be substituted by one Deputy, selected from R7one or two substituents selected from R8and/or tetrazolium, and preferably is a group:

< / BR>
Cyclic unsaturated aliphatic group may be, for example, cyclohexenyl, which may be substituted by 1 to 4 substituents selected from R7and/or 1 or 2 substituents selected from R8and preferably is a group:

< / BR>
< / BR>
Y and Z which are independent from each other, represent-CO - or-CH(OH)-, provided that they are both-CH(OH)-.

R6represents hydroxyl,1- C10-alkoxy, metal oxy group or0- C7the amino group.

WITH1- C10-alkoxy includes, for example, methoxy, atok is iloxi, n-octyloxy, n-nonyloxy, n-deaniacs, cyclopropylamine, cyclobutylamine, cyclopentyloxy, cyclohexyloxy, cycloheptylamine, cyclooctylamine, cyclomaniacs, cyclodecanone, 2-propenyloxy, CIS-2-butenyloxy, TRANS-2-butenyloxy, methacrylate, benzyloxy, o-methylaniline, m-methylaniline, p-methylaniline, phenoxy, on-methylphenoxy, m-methylphenoxy, p-methylphenoxy, 2,3-dimethylphenoxy, 2,4-dimethylphenoxy, 2,5-dimethylphenoxy, 2,6-dimethylphenoxy, 3,4-dimethylphenoxy, 3,5-dimethylphenoxy, -naphthyloxy-naphthyloxy.

OM represents a carboxylate group, and M represents lithium, sodium, potassium, calcium or other3; (where R' is hydrogen, C1- C3-alkyl, C3WITH7-cycloalkyl,2- C5-alkenyl, phenyl or benzyl), preferably, sodium, potassium, ammonium, ammonium, triethylamine, tri-n-Propylamine, tribenzylamine, triphenylamine, tricyclohexyltin or triphenylamine.

WITH0- C7The amino group includes, for example, amino, methylamino, ethylamino, dimethylamino, n-propylamino, out-propylamino, p-butylamino, out-butylamino, sec-butylamino, tert-butylamino, methyl-n-propylamino, methyl-ISO-propylamino, diety is ethyl-n-propylamino, ethyl-ISO-propylamino, n-hexylamine, methyl-n-pentylamine, ethyl-n-pentylamine, ethyl-ISO-butylamino, ethyl-sec-butylamino, ethyl-tert-butylamino, di-n-propylamino, n-propyl-ISO-propylamino, di-ISO-propylamino, cyclopropylamino, cyclobutyl-amino, cyclopentylamine, cyclohexylamine, dicyclohexylamine, N-methyl-N-phenylamino, methylbenzylamine, 1-aziridinyl, 1-astinal, 1-pyrrolidinyl, 1-piperidinyl and 1-pyrrolyl. R7represents a C1- C8-alkyl or C3- C7-cycloalkyl.

WITH1- C8-Alkyl includes, for example, methyl, ethyl, n-propyl, ISO-propyl, n-butyl, ISO-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl and n-heptyl. WITH3- C7-Cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

R8represents phenyl which may be substituted WITH1- C7-alkyl, fluorine, chlorine, or bromine, and which is, for example, phenyl, 3-were, 4-were, 3,5-dimetilfenil, 3-ethylphenyl, 4-ethylphenyl, 3,5-diethylphenyl, 3-methyl-5-ethylphenyl, 3-n-propylphenyl, 4-n-propylphenyl, 3,5-di-n-propylphenyl, 3-ISO-propylphenyl, 4-ISO-propylphenyl, 3,5-di-ISO-propylphenyl, 3-florfenicol, 4-forfinal the sludge or 3.5-dibromophenyl.

The solvent in the reaction can be, for example, an alcohol solvent such as methanol, ethanol, n-propanol or ISO-propanol, a polar solvent, such as acetonitrile, dimethylformamide or dimethyl sulfoxide, a solvent halogen type, such as dichloromethane, 1,1 - or 1,2-dichloroethane, chloroform or carbon tetrachloride, or an ethereal solvent such as diethyl ether, di-n-propyl ether, tetrahydrofuran, 1,3 - or 1,4-dioxane. Preferably used are methanol, dichloromethane, diethyl ether or tetrahydrofuran. More preferably, tetrahydrofuran is used. The reaction can be carried out in the temperature range from -100oC to 80oC, preferably from -70oC to 40oC, more preferably from -10oC to 30oC.

For carrying out this reaction stoichiometry-aminoalkoxide complex (I) is used as a constituting from 1 to 2 equivalents relative to the carbonyl compound (III) or from 2 to 3 equivalents relative to the compound (V). On the other hand, the implementation of this reaction catalytically-amerosport (II) is used in an amount of from 0.1 to 20 mol, preferably from 1 to 10 mol, and boranova reagent can be, for example, included the COP brandreth-butylamine, complex N, N-diethylaniline, complex N, N-diisopropylethylamine, complex barandiaran, complex boron-dimethylaminopyridine, complex boron-ethylmorpholine, complex bromethalin, complex, borane trimethylamine complex borontrifluoride or complex parentreported. Preferably used complex baumaterialien or complex brandimay ether. More preferably used complex balancetransfer. In addition, to facilitate the catalytic reaction, an alcohol solvent such as methanol, ethanol, n-propanol or ISO-propanol, preferably methanol or ethanol, more preferably, methanol, it is better to use the number from 3 to 10 equivalents, more preferably from 3 to 6 equivalents.

To improve SYN-selectivity in asymmetric recovery of 1,3-dicarbonyl compounds can be used metal - containing reagent, such as boron reagent, aluminum - containing reagent, a silicon-containing reagent, tin-containing reagent, phosphorus-containing reagent, such reagent, zinc-containing reagent, magnesium-containing reagent or calcium reagent.

Boron reagent is ibaran or catecholborane, trialkylborane reagent, such as triethylborane, triphenylborane, tri-n-butylborane, tri-sec-butyl-borane or three-tert-butylboron, or dialkylphenols reagent, such as lamellarin, or bicyclo [3.3.1]Nona-9-borane (9-BBN).

Aluminium-containing reagent can be allotriophagy reagent, such as tri-ISO-propoxy aluminum, triethoxy aluminum, tri-n-piperonyl aluminum or three-second-piperonyl aluminum, or alkylalkoxy reagent, such as ataxic diethylaluminum, atoxic di-n-Propylamine or atoxic di-ISO-Propylamine.

Silicon-containing reagent may be, for example, tetraalkoxysilane reagent, such as tetramethoxysilane, tetraethoxysilane, or tetrafunctional, realconsoleonly reagent, such as trimetoksi(methyl)silane, triethoxy(methyl)silane, trimetoksi(phenyl)silane, triethoxy(phenyl)silane, triethoxy(vinyl)silane or chloropropionitrile, diakonessenhuis reagent, such as dimethoxydimethylsilane, diethoxydimethylsilane, dimethoxy(methyl) vinylsilane, diethoxy(methyl)silane, dimethoxy(ethyl)vinylsilane, diethoxy(methyl)vinylsilane, dimethoxydimethylsilane or diethoxydimethylsilane, monoalkanolamines reagent, such as methoxycarbonyl reagent, such as dihydroxydiphenylsulfone, dihydroxyethylene, dihydroxy-di-n-propylsilane, dihydroxy-di-ISO-propylsilane or dihydroxydiphenyl-silane.

Tin-containing reagent may be, for example, alkyl(tin) acetate reagent, such as acetate tri-n-butyanova, diacetate, di-n-butyanova or diacetate di-Ochirova or alkyl(alkoxy)tin-containing reagent, such as dimethyldiethoxysilane, determinationof, di-n-propyltrimethoxysilane, di-ISO-propyltrimethoxysilane, di-ISO-butylcellosolve, di-verbalargumentative or di-tert-butyldiphenoquinone.

Phosphorus-containing reagent may be, for example, triavir phosphoric acid, such as trimethylphosphite, triethylphosphite, tri-ISO-propylphosphine, Tr-n-butylphosphate or triphenylphosphite.

Such a reagent can be, for example, a titanium alkoxide, such as tetraethylorthosilicate, chlorotri-ISO-proportation, Tetra-n-proportation, Tetra-ISO-propoxy titanium or Tetra-n-piperonyl titanium.

Zinc-containing reagent may be, for example, a carboxylate of zinc, such as zinc acetate, zinc propionate or benzoate zinc, a zinc halide such as zinc fluoride, zinc chloride, zinc bromide or Jodi is zinc.

Magnesium-containing reagent may be, for example, a magnesium alkoxide, such as dimethoxy magnesium, detoxed magnesium, di-n-propoxy magnesium or ISO-propoxy magnesium.

Calcium-containing reagent may be, for example, calcium alkoxide, such as dimethoxy calcium, detoxed calcium, di-n-propoxide calcium or ISO-propoxide calcium.

Of these metal-containing reagents are preferred, diethylmethoxyborane, tri-ISO-propoxide aluminum and trichloro-tri-ISO-proportation, and more preferred are diethylmethoxyborane and three-ISO-propoxide aluminum. Metal-containing reagent is used in an amount of 1 to 3 equivalents, preferably 1 to 1.2 equivalents relative to the 1,3-dicarbonyl compound.

In accordance with the present invention, the target optically active 1,3-SYN-dialogue compound of formula (VI) can be synthesized via reduction reaction of 1,3-di-carbonyl compounds of the formula (V), carried out in good yield and high SYN-selectivity by simple procedures with an optically active aminoalkoxide complex of formula (I). Optically active 1,3-SYN-diol (HMG-CoA)). Thus, optically active-aminoalkoxide complex (I) of the present invention can be used to obtain such a typical inhibitors of HMG-CoA reductase, as lovastatin, simvastatin, or pravastatin. In addition, the compound of the present invention can be used to produce optically active alcohols of formula (IV)) of various carbonyl compounds (formula (III) with a good asymmetric output.

A more detailed description of the present invention are provided in the following examples. Note, however, that these examples are only illustrative of the present yobretenie, and should not be construed as a limitation on its scope.

Example 1.

Obtaining optically active derivative of amerosport (II) (Phase a, b and D) Obtaining (S)-N-(-/ naphthyl)methyl-2-pyrrolidineethanol ((S)-II-I)

< / BR>
Stage A. Commercially available ethyl ester of Proline (VII-I) is subjected to a recovery in ethyl ether while cooling with ice, sociallyengaged, resulting in a gain prolinol (VIII-I). Using optically active starting materials obtain the corresponding optically active prolinol (VIII-I).

Stages b and C.

< / BR>
[]2D0= -49,8(c= 0,1, CH3OH). IR-spectrum (KBr)maxcm-1: 3200, 3030, 2950, 2850, 1600, 1580, 1420, 1340, 1180, 1020, 850, 820, 740.1H-NMR (CDCI3)M. D.:7,30-7,83 (7H, m, aromatic.-N), 2,28-to 4.23 (8H, m, other-N), 1,66-1,90 (4H, m,-CH2CH2C).

Obtaining (R)-N-naphthyl)methyl-2-pyrrolidineethanol ((R-II-I)

Similarly, using (R-prolinol ((R)VIII-I) as starting product is obtained R-N-(-naphthyl)methyl-2-pyrrolidineethanol (R-II-I).

< / BR>
[]2D0=+50,7o(c= 0,1, CH3OH). IR-spectrum (KBr)maxcm-1: 3200, 3030, 2950, 2850, 1600, 1580, 1422, 1340, 1180, 1020, 850, 820, 740.1N-YARM (CDCI3)The)-N-(-naphthyl)methyl-2-pyrrolidineethanol ((S)-II-2)

Similarly, using as starting product (S)-prolinol ((S)-VIII-I)and-naphthaldehyde,get(S)-N-(-/ naphthyl)methyl-2-pyrrolidineethanol ((S)-II-2).

< / BR>
[]2D0=-65,6o(C= 0,16, CH3OH). IR-spectrum (NaCl)maxcm-1: 3400, 3040, 2950, 2870, 1600, 1500, 1460, 1350, 1170, 1040, 800, 790, 780.1H-NMR (CDCl3) ppm: 7,25-8,30 (7H, m, aromatic.N), 2,60-4,55 (m, 7H, other H) TO 2.35 (1H, Shir., IT), 1,65 FOR 2.01 (4H, m,-CH2CH2C).

Obtaining (R)-N-(-naphthyl)methyl-2-phenylglycinol ((R)-II-3)

Similarly, using 1,00 g (7,29 mmol) of ((R)-phenylglycinol ((R)-VIII-2)and-naphthaldehyde,poluchaut,g(R)-N-(-naphthyl)methyl-2-phenylglycinol ((R)-11-3) with a quantitative yield.

< / BR>
[]2D0=+3,1o(C= 0,1, CH3OH). 1H-NMR (CDCl3) ppm: 7,30-7,80 (12H, m, aromatic. N), 3,50 - 4,50 (5H, m, other M), 2,30 (1H, Shir., IT), 2,02 (1H, Shir.S.,N).

Example 2.

Obtaining optically active-aminoalkoxide complex (I) (stage E)

Obtain (S)-N-(-naphthyl)methyl-2-pyrrolidinecarbonyl ((S)-I-I)

< / BR>
, 41 g (10 mmol) of (S)-N-(-naphthyl)methyl-2-pyrrolidineethanol ((S)-II-I) is dissolved in 50 ml of anhydrous THF, and then, stirring, added dropwise to 10 ml of tertrahydrofuran ring solution containing 1.0 M compleksoobrazutee hydrogen, the mixture was then stirred for 10 minutes. This bananowy complex used in the form TGFF solution for recovery of carbonyl compounds. Then THF is distilled off at room temperature under reduced pressure to get 2,53 g (100%) of the desired product as a viscous oily substance. This substance has the following physical characteristics: infrared spectrum (KBr)maxcm-1: 3030, 2950, 2850, 2350 (- N), 1600, 1450, 1420, 1360, 1280, 1180, 1030, 850, 820, 750.1H-NMR (CDCl3) ppm: 7,30-7,83 (7H, m, aromatic.N), and 1.00-5,80 (13H, m, other M).

Similarly, using as initial products of the compound ((R)-II-I), ((S)-II-2) and ((R)-II-3), are optically active aminoalkoxide complexes (I), are presented in table. 2.

Comparative example 1. Obtain ethyl (E)-7 [2'-cyclopropyl-4'-(p-forfinal)quinoline-3'-yl]-3,5-dioxo-6-heptanoate

2.35 g (63.1 mmol) of 60% sodium hydride in a stream of nitrogen suspended in 300 ml of dry tetrahydrofuran, and the suspension is stirred for five minutes and then cooled with ice. To the resulting suspension, using an injector, gradually added dropwise 7.47 g (57,4 mmol) ethylacetoacetate and after the termination of the formation of hydrogen the mixture is stirred for 15 minutes. To Polus stirred for 15 minutes. After the yellow color of the reaction solution changed to orange-red, 6,00 g (15.9 mmol) of N-methyl-N-methoxyamine (E) 3-[2'-cyclopropyl-4'(p-forfinal)quinoline-3'-yl] -2-propanolol acid (G. B. Reddy, T. Minami, T. Hanamoto, T. Hiyama, J. Org.Chem., 56, 5754, 1991) was dissolved in 100 ml of dry THF and the resulting solution was added dropwise to the reaction solution. Then the reaction temperature was raised to room temperature and the mixture is stirred for 24 hours. The reaction solution is cooled with ice and the reaction stopped by adding 200 ml of 1 M aqueous solution of acetic acid. The aqueous layer was separated and extracted twice with 200 ml of ethyl acetate. The extract combined with the organic layer and the mixture is washed twice with 50 ml of a saturated aqueous solution of sodium chloride and then dried with anhydrous magnesium sulfate. Then the solvent is distilled off under reduced pressure and the residue purified by column chromatography on silica gel (manifesting solvent: hexane/ethyl acetate=10/1) and then precrystallization from ethyl acetate to obtain 3.11 g of the target compound. MS-spectrum (E1) m/e: 445(M+), 400, 358, 330, 316, 288.1H-NMR (CDCl3) ppm: 7,97-7,19 (8H,m, aromatic.N), 7,71 (1H, d, J=17 Hz, PINE trees,=), 6,03 (1H, d, J=16hz, SOS=CH), the 5.51 (1H, s, enol-olefinic H), IS 4.21 (2H, square, J=7 Hz, SOON23).

Example 3. Catalytic asymmetric recovery monocarbonyl connection with the use of optically active N-naprimer-2-pyrrolidineethanol (compound (II)/NR3)

Carbonyl compound (1 mmol) dissolved in 5 ml of THF and then to the resulting solution was added 192 mg (6 mmol) of methanol and 23 mg (0.1 mmol) of optically active N-naphthylmethyl-2-pyrrolidineethanol (compound (II)). Then to the solution was added 3 ml or 10 ml (3 mmol or 10 mmol) IM BH3THF solution and the mixture is stirred at a temperature of 20oC or 30oC for 6 to 19 hours. To the reaction solution to vysalivaniya add 13 ml of 1 n model HC1 followed by extraction with 100 ml of ethyl acetate. Then the extract was washed with 10 ml saturated aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate. Then the solvent is distilled off under reduced pressure and the resulting liquid is purified by thin-layer chromatography for isolation and target optically active alcohol with quantitative yield.

In table. 3 presents the results of the asymmetric recovery of various monocarbonyl compounds with an optically active N-naphthylmethyl-2-pyrrole alcohol, are determined by comparison with optically active standard product by conversion of the alcohol product in urethane diastereoisomer, subsequent analysis of liquid chromatography high resolution (IHVR) on silica gel using a column CHIRALCEL OD (Daicel Chemical Industries, Ltd.). or method Lamed et al., (E. Keinan, E. K. Hafeli, K. K. Seth & R. Lamed, J. Am.Che.Soc., 108, 162 (1986)).

In the reaction of asymmetric recovery monocarbonyl compound (III), the compound (I) of the present invention, providing a high asymmetric yield, was used in a catalytic amount, without selection, i.e. in the form in which it was formed in the reaction system by using the compound (II). In the case of a conventional asymmetric recovery using 2-hexanone as substrate (J. Chem.Soc.Perkin Trans.1., 2887 (1984), J. Org.Chem. 49, 555 (1984)), even if bananowy complex is used in stoichiometric quantities, asymmetric output accounted for only 25% (bananowy complex having a polymer Deputy, entered nitrogen ((S)-Proline) or 55% (S)-2-amino-3-methyl-1,1-diphenylbutane-1-ol-bananowy complex). Thus, the advantage of the compounds of the present invention is obvious.

Example 4.

Asymmetric recovery of 1,3-dicarbonyl compounds (I) with the use of various optically active, aminoethoxyethanol comp is given in 1 ml solution in THF 1.0 M of diethylmethoxyborane or 1 mmol (204,3 mg), tri-ISO-propoxide aluminum. Set the temperature of the mixture equal to from -78oC to 20oC in a stream of nitrogen gas.

To this solution of 1,3-dicarbonyl compounds (V) are added dropwise (S)-N-(-naphthyl)methyl-2-pyrrolidinylcarbonyl complex ((S)-I-I) obtained according to the dreamer 2, and the mixture is stirred for 3 hours. On the other hand, for education boranova complex in the reaction system, (S)-N-(-nafti)methyl-2-pyrrolidineethanol ((S-I-I), obtained in example I, or THF-solution of various optically active aminoalcohols (from 0.1 to 3 mmol) is added dropwise from 2 to 10 ml (2 to 10 mmol) of 1.0 M solution NR3THF. This solution is added dropwise to vysheukazannoe 1,3-dicarbonyl compound (Y) and the mixture is stirred for from 3 to 28 hours. In the case of catalytic amounts of amerosport, in addition, added 192 mg (6 mmol) of methanol.

Then to the reaction solution was added to 540.5 mn (9 mmol) of acetic acid and the mixture is diluted with 300 ml ethyl acetate, washed with 20 ml saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent is distilled off under reduced pressure and to the resulting orange-red liquid was added 1 l of methanol and the mixture is heated in the course is idcast purified by column chromatography on silica gel to obtain the desired optically active 1,3-cindylouwho compound (VI-I). The definition of asymmetric output (%) is carried out using liquid chromatography high resolution (IHVR) using a column CHIRALCEL OD, manufactured by Daicel Chemical Industries, Ltd.

With regard to reducing agents, are presented in table. 4-aminoalkoxide complex (S)-I-1) used in the tests NN1 - 3. In tests NN 4 - 9 used-aminoalkoxide complex formed in the reaction system using amerosport. In test # 5 and test # 6). use a catalytic amount of amerosport ((S-11-1). In addition, in the test No. 6 as a solvent used dichloromethane.

Comparative example 1. The procedure was carried out in the same manner as in example 4, using conventional Baranovich complexes. The results are presented in table. 5.

Example 5.

50 mg (0.27 mmol) of ethyl 3,5-dioxo-6-heptynoate dissolved in 5 ml of THF and 52 ml of methanol. Then, without adding or adding a three-ISO-propoxide aluminum as the metal reactant, the reaction is carried out for 20 hours at 20oC with the use of 5.4 ml of a 1.0 M solution NR3THF and 6.2 mg (0,027 mmol) of (S)-N-(-naphthyl)methyl-2-pyrrolidineethanol (connection (S)-11-1) obtained in example 1, the h/SUB>) ppm:/ 4,81 (1H, Shir. , -CH-OH), 4,17 (2H, square, J=7 Hz, SOON2), of 3.60 (1H, m,-CH(OH) -), TOTALING 3.04 (1H, s,=C-H), 1,50-1,65 (6N, m, other M) and 1.3 (3H, t, J=7 Hz, SOON2CH3). IR (NaCl) cm-1: 3400 (OH), 2220(C=C), 1720 (C=0),

1. Optically active-aminoalkoxide complex of the formula I

< / BR>
where R1- C1- C8alkyl or C7- C11aralkyl, R2- C1- C8alkyl, C3- C7cycloalkyl or C7- C11aralkyl, or R1and R2together form a (CH2)nwhere n is 3 or 4;

Ar is naphthyl, antrel or tenantry, which may be substituted by 1 to 3 substituents selected from the group comprising halogen, C1- C6alkyl, C6- C10aryl and C1- C6alkoxy.

2. Optically active-aminopyrene derivative of the formula II

< / BR>
where R1- C1- C8alkyl or C7- C11aralkyl;

R2- C1- C8alkyl, C3- C7cycloalkyl or C7- C11aralkyl, or R1and R2together form a (CH2)nwhere n is 3 or 4;

Ar is naphthyl, antrel or tenantry, which may be substituted by 1 to 3 substituents selected from the group comprising halogen, C1- C6is not C1- C8the alkyl, or when Ar represents tenantry, R1and R2do not form together (CH2)3.

3. A method of obtaining optically active-aminoalkoxide complex of formula (I) specified in paragraph 1, which consists in the interaction of optically active-aminopyrrolo derivative of the formula IX

< / BR>
where R1represents a C1- C8alkyl or C7- C11aralkyl, R2represents a C1- C8alkyl, C3- C7cycloalkyl or C7- C11aralkyl, or R1and R2together form a (CH2)nwhere n is 3 or 4;

Ar represents naphthyl, antrel or tenantry, which may be substituted by 1 to 3 substituents selected from the group comprising halogen, C1- C6alkyl, C6- C10aryl or C1- C6alkoxy,

with boranova reagent, such as selected from the group including, for example, a complex of borane-tetrahydrofuran, borane complex-diethyl ether complex, borane-pyridine complex borane-ammonia complex, borane-tert-butylamine, complex, borane - N,N-diethylaniline, complex, borane - N,N-diisopropylethylamine, complex, borane-dimethylamine complex borane-4-d is a complex of borane-triphenylphosphine complex and borane-4-triphenylphosphite.

4. A method of obtaining optically active alcohols of the General formula IV

< / BR>
where R3and R4differ from each other and represents a C1- C10alkyl, C2- C10alkenyl, C2- C10quinil, C6- C14aryl, or R3and R4together form a 5-6-membered cycle, which is condensed with benzene ring;

* indicates an optically active center,

by stereoselective recovery carbonyl derivative of formula III

< / BR>
where R3and R4above,

in the presence of an optically active catalyst, characterized in that the optically active catalyst is used-aminoalkoxide complex, as such or formed in the reaction system of the optically active aminopyrrolo derivative of the formula (IX) and boranova reagent specified in paragraph 3, in the process of recovery.

5. A method of obtaining optically active alcohol compounds of formula (VI - 1)

< / BR>
where R6- C1- C10alkoxy;

R7- C1- C7alkyl or C3- C7cycloalkyl;

R8is phenyl which may be substituted by fluorine, chlorine or bromine;

* denotes optic to each other,

by stereoselective recovery of 1,3-dicarbonyl compounds in the presence of an optically active catalyst, characterized in that as a 1,3-dicarbonyl compound is used as a compound of General formula (V - 1)

< / BR>
where R6, R7and R8above,

and as optically active catalyst is used-aminoalkoxide complex, specified in paragraph 1, as such or formed in the reaction system of the optically active aminopyrrolo derivative of the formula (IX) and boranova reagent specified in paragraph 3, in the process of recovery.

6. A method of obtaining optically active 1,3-SYN-delovogo derivative of the formula (VI - 2)

< / BR>
where R5is hydrogen;

R6- C1- C10alkoxy;

* indicates an optically active center, provided that the two optically active center take SYN-conformation with respect to each other,

by stereoselective recovery unsaturated carbonyl compounds in the presence of complex boron-containing catalyst, characterized in that as unsaturated carbonyl compounds using 1,3-dicarbonyl derivative of the formula (V - 2)

< / BR>
where Rwho bananowy complex, specified in paragraph 1, as such or formed in the reaction system of the optically active aminopyrrolo derivative of the formula (IX) and boranova reagent specified in paragraph 3, in the recovery process.

 

Same patents:

The invention relates to a new method of obtaining sulfur-containing imidazole derivatives of General formula (I) possess valuable pharmacological properties, and new intermediate products of the formula III, IV and V

(I)

where

R1- C1-C4-alkyl;

R2- alkylthiol containing 1-4 carbon atoms, possibly substituted by one or more substituents selected from halogen, hydroxyl, alkoxy, benzyloxy, and means phenylthio or mercapto;

R3- carboxyl, free or converted into a salt or an ester of linear or branched C1-C4-alkyl, or hydroxyalkyl;

R4- radical (CH2)m-SO2-X-R10where X is - NH-, NHCONH-, NHCO-O-; R10is hydrogen or C1-C3-alkyl, m = 0, 1;

the interaction of imidazole formula II

(II)

with the corresponding halogen derivatives - a compound of formula III

(III)

where

B is a boron atom;

X1and X2is hydroxyl or X1with X2form together with the boron atom to which they relate, zatem subjected to interaction with the compound of the formula V

(V)

where

X4is a halogen atom
The invention relates to the field of production of granulated materials having a low melting point and decomposition, such as dimethylaminoborane, which is a reducing agent used in organic synthesis and nonelectric plating

The invention relates to the technology for dimethylaminoborane (DMAB) by a reaction between dimethylamine with gaseous DIBORANE
The invention relates to the production of stable dimethylaminoborane (DMAB) and, specifically to the technology of its cleaning products

The invention relates to new chemical compounds with antimicrobial and antifungal activity

The invention relates to a method for producing 1,1-dimethyl-4,4-dipyridine of dicarbonate formula I

H3CNNCH32C2B9H12which can be used as a component for electrochromic composition

The invention relates to the field of production of preservative to protect the wood from rot and mold, more specifically to methods for boric esters of polyhydric alcohols, which antiseptics

The invention relates to the field of production of preservative to protect the wood from rot and mold, more specifically to methods for boric esters of polyhydric alcohols, which antiseptics

The invention relates to certain derivatives of piperidine, the way its receipt, to compositions containing these compounds and to their use as fungicides

The invention relates to organic chemistry, specifically to new chemical compounds, of General formula:

< / BR>
in particular 1,3-bis(2'-hydroxy-3'-morpholinopropan)-6-methyluracil(a); 1,3-bis(2'-hydroxy-3'-piperidinoethyl)-6-stands-rallu (b); 3-bis(2'-hydroxy-3'-morpholinopropan)-5-hydroxy-6-methyluracil (); 1,3-bis(2'-hydroxy-3'-piperidinoethyl)- 5-hydroxy-6-methyluracil (g); 1,3-bis(2'-hydroxy-3'-morpholinopropan)-5-(2'-hydro - XI-3'-morpholinoethoxy)-6 - methyluracil (d) and 1,3-bis(2'-hydroxy-3'-piperidinoethyl)-5-(2'-hydroxy-3'-piperidino - poxy)- 6-methyluracil (E), showing immunotropic and anti-inflammatory activity

The invention relates to 1,4-disubstituted the piperazines of General formula (I), which means the group-CO - or-CH2-OCO; D - heteroaryl selected from a range including 1, 3, 5-triazinyl, pyrimidinyl and pyridinyl, possibly substituted by one or two substituents selected from a range, including mono-(C1-C6)-alkylamino, mono-(C3-C7)- alkynylamino-, di-(C1-C6)-alkylamino-,

(C1-C6)-alkyl-(C3-C7)-alkylamino and pyrrolidin-I-yl group; Raand Rbis a hydrogen atom or (C1-C3)-alkyl; n is an integer from 1 to 4; their enantiomers, racemic mixtures and their salts with pharmaceutically acceptable acids and bases

The invention relates to heterocyclic amines of formula I:

,

in which

X represents-CH2-group or-S-group;

B denotes a group selected from a number containing-CO -, - CH2OCO-, -CH2OCS-, -CH2NHCO - CH2NHCS-group;

D represents benzhydryl or phenyl group, optionally substituted by halogen atoms, and heterocyclic group, selected from a number containing 1,3,5-triazine-2-yl, pyridin-2-yl and pyrimidine-4-yl, and optionally substituted by one or two substituents selected from the group comprising amino, mono - or di-(C1C6) alkylamino, mono- (C3-C7)-alkynylamino, mono-(C3-C7)-quinil-amino group and pyrrolidin-1-yl group;

The is a simple carbon-carbon bond or a group of the formula: -CH2CH2or CRaRb-, where Raand Rbis a hydrogen atom, (C1-C3)alkyl, or taken together with the carbon atom to which they are attached, form a (C3-C6) cycloalkyl;

A is selected from the group comprising (a) carboxyl group optionally esterified (C1-C4) Ukrspirt the crystals: -CОNHRgOH, where Rcand Rdidentical or different, represent a hydrogen atom, (C1-C6) alkyl, benzyl, pyridin-2-yl, or taken together with the nitrogen atom to which they are bound, form piperidino, morpholino-, 4-thiomorpholine-, 4,5-diazepino, 4-(C1-C4)alkylpiperazine; Rfis a tolyl; Rgis a (C1-C4) alkyl;

(b) (C1-C3) alkyl;

(c) the group-NRcRdwhere Rcand Rddefined above,

(d) a cyano, if "y" does not mean a simple carbon-carbon bond

in the form of S-enantiomers, diastereomers, in the form of various racemic mixtures and their salts with pharmaceutically acceptable acids and bases

The invention relates to new chemical compound, specifically, to hydrotartrate CIS-(3-methyl-2(1-hydroxy-propyl)/pyrrolidine formula I

HCH2)3OH--()2-COOH with astragalina activity
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