Esters of n-substituted 14-hydroxymorphinone and method of production thereof

 

The invention relates to organic chemistry, particularly to esters of N-substituted 14-hydroxymorphinone that are important narcotic analgesic and/or antagonistic means - opiate receptor blockers prolonged action and to methods for their preparation. Describes esters of N-substituted 14-hydroxymorphinone General formula where R is allyl, cyclopropylmethyl, R' is chosen from the group consisting of acid residues: -C19-C25- aliphatic carboxylic acid, -C19-C25- unsaturated carboxylic acids with one double bond, -C10-C15polyunsaturated carboxylic acids with 2 to 3 double bonds, -C10-C15unsaturated acids with a triple bond, the formula NS=C-CH2-(CH2)n-CH2-COOH, where n=5-10, alkyl substituted cyclopropane-, dicyclopropyl and tricyclopentadiene acids, where Ala - 4-15 carbon atoms, cycloaliphatic carboxylic acids selected from the group of cyclopentane, cyclohexane, Cycloheptane-, cyclooctanone acids or their alkyl derivatives, where Ala - 2-3 carbon atoms; polycyclic carboxylic acids with mating cycles selected from the group bicyclohexyl-bicycloheptane-gruppy; alkyl substituted frame carboxylic acids, where ALK-N, C1-C8; heterocyclic acids and acids with mixed functions, R" represents H or choose from a group of these acid residues equal to the values of R' or different from them. Also describes how to obtain esters of N-substituted 14-hydroxymorphinone. The technical result - obtaining high yields of final product and simplify the way they are received. 3 c. and 6 C.p. f-crystals, 6 PL.

Description text in facsimile form (see graphic part).

Claims

1. Esters of N-substituted 14-hydroxymorphinone General formula I (see graphic part) where R is allyl, cyclopropylmethyl; R' is selected from the group consisting of acid residues: -C19-C25- aliphatic carboxylic acids; -C19-C25- unsaturated carboxylic acids with one double bond; -C10-C18polyunsaturated carboxylic acids with 2 to 3 double bonds, -C10-C15unsaturated acids with a triple bond, the formula NS= C-CH2-(CH2)n-CH2-COOH, where n= 5-10; alkyl substituted cyclopropane-, dicyclopropyl and tricyclopentadiene acids, gden-, Cycloheptane-, cyclooctanone acids or their alkyl derivatives, where Ala - 2-3 carbon atoms; polycyclic carboxylic acids with mating cycles selected from the group bicyclohexyl-bicycloheptane-tricyclodecane acids, and spiranovic carboxylic acid; R' substituted aromatic carboxylic acids, where R"' is alkyl-, alkoxy - or cyclopropylmethyl group; alkyl substituted frame carboxylic acids, where ALK - N, C1-C8; heterocyclic acids and acids with mixed functions; R" represents H or choose from a group of these acid residues equal to the values of R' or different from them.

2. The method of obtaining esters of N-substituted 14-hydroxymorphinone General formula II (see graphic part) where R is allyl, cyclopropylmethyl, R" is H; R' is selected from the group consisting of acid residues: -C19-C25- aliphatic carboxylic acids; -C19-C25- unsaturated carboxylic acids with one double bond; -C10-C18polyunsaturated carboxylic acids with 2 to 3 double bonds; -C10-C15unsaturated acids with a triple bond, the formula NS= C-CH2-(CH2)n-CH2-COOH, where n= 5-10; alkyl substituted cyclopropane-,s acid, selected from the group of cyclopentane, cyclohexane, Cycloheptane-, cyclooctanone acids or their alkyl derivatives, where Ala - 2-3 carbon atoms; polycyclic carboxylic acids with mating cycles selected from the group bicyclohexyl-bicycloheptane-tricyclodecane acids, and spiranovic carboxylic acid; R' substituted aromatic carboxylic acids, where R"' is alkyl-, alkoxy - or cyclopropylmethyl group; alkyl substituted frame carboxylic acids, where ALK - N, C1-C8; heterocyclic acids and acids with mixed functions, by reacting N-substituted 14-hydroxymorphinan with allermuir agent in the presence of acceptor galgenwaard - carbonate or bicarbonate of an alkali metal in the environment of an organic solvent, characterized in that the interaction is subjected to 10-35% aqueous solution of N-substituted 14-hydroxymorphinan hydrochloride, and as Alliluyeva agent use the anhydrides of the acids selected from the group of these acids, the reaction of lead in the environment of water-immiscible chlorinated aliphatic hydrocarbon, in the presence of an aqueous solution of acceptor galgenwaard.

3. The method of obtaining esters of N-substituted 14-forward way of obtaining esters of N-substituted 14-hydroxymorphinone by p. 2, characterized in that as chlorinated hydrocarbons using methylene chloride, chloroform, dichloroethane, and trichloroethylene.

5. The method of obtaining esters of N-substituted 14-hydroxymorphinone General formula III (see the graphical part) where R is allyl, cyclopropylmethyl; R' is selected from the group consisting of acid residues: -C19-C25- aliphatic carboxylic acids; -C19-C25- unsaturated carboxylic acids with one double bond; -C10-C18polyunsaturated carboxylic acids with 2 to 3 double bonds; -C10-C15unsaturated acids with a triple bond, the formula NS= C-CH2-(CH2)n-CH2-COOH, where n= 5-10; alkyl substituted cyclopropane-, dicyclopropyl and tricyclopentadiene acids, where Ala - 4-15 carbon atoms, cycloaliphatic carboxylic acids selected from the group of cyclopentane, cyclohexane, Cycloheptane-, cyclooctanone acids or their alkyl derivatives, where Ala - 2-3 carbon atoms; polycyclic carboxylic acids with mating cycles selected from the group bicyclohexyl-bicycloheptane-tricyclodecane acids, and spiranovic carboxylic acid, R"' substituted aromatic carboxylic acids, where R"' is alkyl, ALK is; heterocyclic acids and acids with mixed functions, R" is selected from the group of these acid residues equal to the values of R' or different from them,
by reacting N-substituted 14-hydroxymorphinan with allermuir agent in the presence of acceptor galgenwaard - carbonate or bicarbonate of an alkali metal in the environment of an organic solvent, characterized in that the interaction is subjected to 10-35% aqueous solution of N-substituted 14-hydroxymorphinan hydrochloride by sequential two-stage processing of the last allermuir agent selected from the group of anhydrides of these acids, with each stage are in the environment of water-immiscible chlorinated aliphatic hydrocarbon, in the presence of an aqueous solution of acceptor galgenwaard.

6. The method of obtaining esters of N-substituted 14-hydroxymorphinone under item 5, characterized in that as Alliluyeva agent use the same or different acid chlorides of the acids.

7. The method of obtaining esters of N-substituted 14-hydroxymorphinone under item 5, characterized in that use 10-20% solution of the carbonate of an alkali metal.

8. The method of obtaining esters of N-substituted 14-hydroxymorphinone . the procedure of obtaining esters of N-substituted 14-hydroxymorphinone under item 5, characterized in that as a chlorinated hydrocarbon used methylene chloride, chloroform, dichloroethane, and trichloroethylene.

 

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