Unlock instant, AI-driven research and patent intelligence for your innovation.

The method for reclaiming valsartan methyl ester from valsartan crystallization mother liquor

A technology of valsartan methyl ester and crystallization mother liquor, which is applied in the solid field of valsartan methyl ester, can solve problems such as difficulty in management, and achieve the effects of reducing raw material costs and easy operation

Active Publication Date: 2017-08-01
LIVZON GROUP CHANGZHOU KONY PHARMA
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The most ideal recovery method is to directly recover valsartan from the valsartan crystallization mother liquor, but because it contains more chiral isomers of valsartan, the recovery of valsartan requires multiple recrystallization treatments to meet the quality requirements. requirements, and how the recovered valsartan complies with the GMP standard also has certain management difficulties

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • The method for reclaiming valsartan methyl ester from valsartan crystallization mother liquor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Take 200ml of valsartan ethyl acetate crystallization mother liquor theoretically containing 10g of valsartan, wash with pH=3-4 hydrochloric acid aqueous solution 3 times, 100ml each time, and then dry and dehydrate with anhydrous sodium sulfate for 30 minutes. Filtrate, wash and combine the filtrates, concentrate under reduced pressure, dissolve the distillation residue with 100ml of toluene, add 20ml of methanol and 1ml of concentrated sulfuric acid after dissolving, keep the reaction at 75-85°C, follow the reaction by TLC until the valsartan spots disappear. Cool down to room temperature, wash with water twice, 30ml each time, then extract twice with 2% sodium hydroxide solution below 10°C, 50ml each time, combine the alkaline aqueous phase, adjust pH=1.5~ with hydrochloric acid below 10°C 2.5, extract twice with methyl tert-butyl ether, 40ml each time, combine the extracts, dry and dehydrate with anhydrous sodium sulfate for 30 minutes. Filtrate, wash and filtrate c...

Embodiment 2

[0026] Take 200ml of valsartan ethyl acetate crystallization mother liquor theoretically containing 10g of valsartan, wash with pH=3-4 hydrochloric acid aqueous solution 3 times, 100ml each time, and then dry and dehydrate with anhydrous sodium sulfate for 30 minutes. Filtrate, wash and combine the filtrates, concentrate under reduced pressure, dissolve the distillation residue with 100ml of toluene, add 20ml of methanol and 1ml of concentrated sulfuric acid after dissolving, keep the reaction at 75-85°C, follow the reaction by TLC until the valsartan spots disappear. Cool down to room temperature, wash with water twice, 30ml each time, then extract twice with 2% sodium hydroxide solution below 10°C, 50ml each time, combine the alkaline aqueous phase, adjust pH=1.5~ with hydrochloric acid below 10°C 2.5, extract twice with isopropyl ether, 60ml each time, combine the extracts, dry and dehydrate with anhydrous sodium sulfate for 30 minutes. Filtrate, wash and filtrate combined,...

Embodiment 3

[0028] Take 200ml of valsartan ethyl acetate crystallization mother liquor theoretically containing 10g of valsartan, wash with pH=2-3 hydrochloric acid aqueous solution 3 times, 100ml each time, and then dry and dehydrate with anhydrous sodium sulfate for 30 minutes. Filtrate, wash and combine the filtrates, concentrate under reduced pressure, dissolve the distillation residue with 100ml of toluene, add 20ml of methanol and 1ml of concentrated sulfuric acid after dissolving, keep the reaction at 75-85°C, follow the reaction by TLC until the valsartan spots disappear. Cool down to room temperature, wash with water twice, 30ml each time, then extract twice with 2% sodium hydroxide solution below 10°C, 50ml each time, combine the alkaline aqueous phase, adjust pH=1.5~ with hydrochloric acid below 10°C 2.5, extract twice with methyl tert-butyl ether, 40ml each time, combine the extracts, dry and dehydrate with anhydrous sodium sulfate for 30 minutes. Filtrate, wash and combine th...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a method for recycling valsartan methyl ester from valsartan crystallization mother solution. The method comprises the following steps of: washing the valsartan crystallization mother solution by using acid aqueous solution, drying, dehydrating, and filtering; distilling filtrate, recycling ethyl acetate in the valsartan crystallization mother solution, dissolving distillation residues by using a solvent I, adding methanol and a catalyst, keeping the temperature, and reacting; washing by using water after keeping the temperature; extracting by using sodium hydroxide solution; adjusting alkaline extraction liquid to acidity, and extracting by using a solvent II; and drying and dehydrating the extraction liquid, dropping in a solvent III, crystallizing, and separating out valsartan methyl ester solids. The method disclosed by the invention has the beneficial effects that: the cost of a raw valsartan material can be effectively reduced; and the method is simple and convenient to operate, and is applied to large-scale industrial production.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a method for preparing valsartan in valsartan mother liquor into solid valsartan methyl ester. Background technique [0002] Valsartan is a new generation of angiotensin Ⅱ receptor antagonist, with high selectivity and special direct action, can effectively antagonize AT1 receptor, its half-life is about 9 hours, and the antihypertensive effect can be maintained for more than 24 hours, and has Good peak-to-trough ratio, has a wide range of therapeutic effects, and is well tolerated by patients. It is the first-line drug for the treatment of hypertension. [0003] At present, the widely used valsartan production process is to prepare valsartan methyl ester first, and then obtain valsartan through hydrolysis reaction, and a partial racemization reaction will occur during the hydrolysis reaction to generate valsartan chiral isomers . In order to reduce the content of ch...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D257/04
CPCC07D257/04
Inventor 陈敖李鸣海黄建明曹忠伟陈兰萍
Owner LIVZON GROUP CHANGZHOU KONY PHARMA