Method for preparing lisinopril intermediate

Patent metadata

Field	Value
Publication number	US-10633329-B2
Application number	US-201716461589-A
Country	US
Kind code	B2
Filing date	Nov 17, 2017
Priority date	Nov 17, 2016
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

A method for preparing a lisinopril intermediate is provided. The method includes: treating (R)-hydroxy-4-phenylbutyrate with sulfonyl chloride in an organic solvent in the presence of a base to obtain a solution of sulfonate; reacting the obtained solution with a salt of trifluoroacetyl lysine; and obtaining a N2-[1-(S)-alkoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine by separating after the reaction is completed. The method provided has a shorter synthesis route, is easy to operate, has a low cost, and is suitable for industrial production.

First claim

The invention claimed is:

1. A preparation method of N 2 -[1-(S)-alkoxycarbonyl-3-phenylpropyl]-N 6 -trifluoroacetyl-L-lysine (II),

wherein the method comprises the following steps:
(a) treating (R)-2-hydroxy-4-phenylbutyrate (I) with a sulfonyl chloride (III) in an organic solvent in the presence of a base to obtain a solution of sulfonate of formula (I);

(b) reacting the solution prepared above with a salt of trifluoroacetyl lysine, and obtaining the compound represented by formula (II) by a separation after the reaction is completed,
in the above formulas:
R 1 is selected from C 1 -C 5 alkyls;
R 2 is selected from C 1 -C 3 alkyls or substituted alkyls, C 6 -C 7 aryls or substituted aryls.

2. The preparation method according to claim 1 , wherein, R 1 is selected from the group consisting of methyl, ethyl and isopropyl.

3. The preparation method according to claim 1 , wherein, the organic solvent described in step (a) is selected from the group consisting of C 2 -C 7 ethers, C 2 -C 4 halogenated alkanes, C 7 -C 10 aromatic compounds and a mixed solvent of any two thereof.

4. The preparation method according to claim 1 , wherein, the mass-to-volume ratio of (R)-2-hydroxy-4-phenylbutyrate (I) to the organic solvent in step (a) is 1 g:2-20 mL.

5. The preparation method according to claim 1 , wherein, the base is selected from the group consisting of carbonates or bicarbonates of alkali metals, C 5 -C 8 pyridine compounds, C 4 -C 9 secondary or tertiary amines.

6. The preparation method according to claim 1 , wherein, the molar ratio of the base to (R)-2-hydroxy-4-phenylbutyrate (I) is 1-10:1.

7. The preparation method according to claim 1 , wherein, the sulfonyl chloride (III) is selected from the group consisting of methylsulfonyl chloride, trifluoromethylsulfonyl chloride, p-nitrobenzenesulfonyl chloride and p-toluenesulfonyl chloride.

8. The preparation method according to claim 1 , wherein, the molar ratio of the sulfonyl chloride (III) to (R)-2-hydroxy-4-phenylbutyrate represented by formula (I) is 1-5:1.

9. The preparation method according to claim 1 , wherein, the temperature range within which the sulfonyl chloride is added is from −5° C. to 15° C.; the range of the reaction temperature of step (a) is 20-60° C.

10. The preparation method according to claim 1 , wherein, the salt of trifluoroacetyl lysine is selected from the group consisting of alkali metal salts of trifluoroacetyl lysine, C 4 -C 12 quaternary ammonium salts of trifluoroacetyl lysine.

11. The preparation method according to claim 1 , wherein, the molar ratio of the salt of trifluoroacetyl lysine to (R)-2-hydroxy-4-phenylbutyrate (I) is 1-6:1.

12. The preparation method according to claim 1 , wherein, the range of the reaction temperature of step (b) is 10-80° C.

13. The preparation method according to claim 1 , wherein, the method further comprises crystallizing the crude compound represented by formula (II) obtained by separation in a crystallization solvent, the crystallization solvent is selected from the group consisting of methanol, ethanol, ethyl acetate, isopropyl acetate, methyl tertiary butyl ether, n-hexane, n-heptane, cyclohexane or a mixed solvent of any two thereof; the mass-to-volume ratio of (R)-2-hydroxy-4-phenylbutyrate (I) to the crystallization solvent used is 1 g:2-20 mL; the range of crystallization temperature is from −5° C. to 60° C.

14. The preparation method according to claim 1 , wherein, the organic solvent described in step (a) is tetrahydrofuran, 2-methyltetrahydrofuran, dichloromethane, toluene, xylene or a mixed solvent of any two thereof.

15. The preparation method according to claim 1 , wherein, the mass-to-volume ratio of (R)-2-hydroxy-4-phenylbutyrate (I) to the organic solvent in step (a) is 1 g: 5-10 mL.

16. The preparation method according to claim 1 , wherein, the base is selected from sodium carbonate, potassium carbonate, sodium bicarbonate, pyridine, 2,6-lutidine, triethylamine, diisopropylamine.

17. The preparation method according to claim 1 , wherein, the molar ratio of the sulfonyl chloride (III) to (R)-2-hydroxy-4-phenylbutyrate represented by formula (I) is 1.1-3:1.

18. The preparation method according to claim 1 , wherein, the temperature range within which the sulfonyl chloride is added is from −5° C. to 10° C.; the range of the reaction temperature of step (a) is 20-40° C.

19. The preparation method according to claim 1 , wherein, the salt of trifluoroacetyl lysine is selected from a lithium salt of trifluoroacetyl lysine, a sodium salt of trifluoroacetyl lysine, a tetramethylammonium salt of trifluoroacetyl lysine.

20. The preparation method according to claim 1 , wherein, the range of the reaction temperature of step (b) is 20-60° C.

Assignees

• Zhejiang Huahai Pharm Co Ltd
• Zhejiang Huahai Tiancheng Pharmaceuticals Co Ltd
• Zhejiang Huahai Licheng Pharmaceuticals Co Ltd
• Zheijiang Huahai Tiancheng Pharmaceuticals Co Ltd

Inventors

• Wang Songqing
• Dong Peng
• Zheng Yang
• Li Quanjun

Classifications

• C07C227/08 Primary

  by reaction of ammonia or amines with acids containing functional groups · CPC title

• C07C303/28

  by reaction of hydroxy compounds with sulfonic acids or derivatives thereof · CPC title

• C07B2200/07

  Optical isomers · CPC title

• C07C229/36 Primary

  with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton · CPC title