Check patentability & draft patents in minutes with Patsnap Eureka AI!

Method for preparing racecadotril through one-pot process

A technology for racecadotril and benzyl, which is applied to the field of one-pot preparation of racecadotril, can solve the problems of occupying production equipment, affecting production efficiency, prolonging production cycle, etc. less reaction

Active Publication Date: 2019-03-08
SHANDONG QIDU PHARMA
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The use of these halogenated reagents causes the route to require complicated post-processing before it can be applied to subsequent reactions, thus occupying production equipment, prolonging the production cycle, and affecting production efficiency

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
  • Method for preparing racecadotril through one-pot process
  • Method for preparing racecadotril through one-pot process
  • Method for preparing racecadotril through one-pot process

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The method for preparing racecadotril by the one-pot method comprises the following steps:

[0037] In the 2000mL reaction bottle, add the mixed solution (V 二氯甲烷 / V 四氢呋喃 =1 / 0.5), lower the temperature, and after controlling the temperature in the reaction flask to -15°C, slowly add 35g of triphosgene to the reaction flask; after the addition, control the temperature in the reaction flask to -15°C, and continue to stir for 5 hours. Then the temperature was lowered, the temperature in the reaction flask was controlled to -55° C., and 119 g of glycine benzyl ester p-toluenesulfonate was slowly added into the reaction flask. Control the temperature in the reaction bottle to -55°C, continue to stir for 2 hours, then start to raise the temperature slowly. When the temperature rose to -35°C, the temperature rise was stopped, and the temperature was controlled at -35°C and stirred for 9 hours. Then it was slowly raised to room temperature, and the organic phase was sequentia...

Embodiment 2

[0039] The method for preparing racecadotril by the one-pot method comprises the following steps:

[0040] In the 2000mL reaction bottle, add the mixed solution (V 二氯甲烷 / V 四氢呋喃 =1 / 1, lower the temperature, and after controlling the temperature in the reaction bottle to -18°C, slowly add 40g of triphosgene to the reaction bottle; after the addition, control the temperature in the reaction bottle to -18°C, and continue stirring for 5.5 hours. Then the temperature was lowered, the temperature in the reaction flask was controlled to -50° C., and 122 g of glycine benzyl ester p-toluenesulfonate was slowly added into the reaction flask. Control the temperature in the reaction bottle to -50°C, continue to stir for 1 hour, then start to raise the temperature slowly. When the temperature rose to -30°C, the temperature rise was stopped, and the temperature was controlled at -30°C and stirred for 8 hours. Then it was slowly raised to room temperature, and the organic phase was sequent...

Embodiment 3

[0042] The method for preparing racecadotril by the one-pot method comprises the following steps:

[0043] Add the mixed solution (V 二氯甲烷 / V 四氢呋喃=1 / 1.5), lower the temperature, and after controlling the temperature in the reaction flask to -20°C, slowly add 38g of triphosgene to the reaction flask; after the addition, control the temperature in the reaction flask to -20°C, and continue to stir for 6 hours. Then the temperature was lowered, the temperature in the reaction flask was controlled to -52° C., and 125 g of glycine benzyl ester p-toluenesulfonate was slowly added into the reaction flask. Control the temperature in the reaction bottle to -52°C, continue to stir for 1.5 hours, then start to slowly increase the temperature. When the temperature rose to -32°C, the temperature was stopped, and the temperature was controlled at -32°C and stirred for 8.5 hours. Then it was slowly raised to room temperature, and the organic phase was sequentially washed with saturated sodi...

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 belongs to the technical field of drug synthesis, and particularly relates to a method for preparing racecadotril through a one-pot process. The method comprises the followings steps: firstly, adding 2-benzyl-3-ethanethioyl crylic acid, organic alkali and a solvent into a reaction container, reducing the temperature to minus 20 to minus 15 DEG C, adding triphosgene solid into the reaction container, and performing temperature control stirring for 5 to 6 hours, so as to obtain a 2-benzyl-3-ethanethioyl acryloyl chloride solution; secondly, reducing the temperature of the 2-benzyl-3-ethanethioyl acryloyl chloride solution to minus 55 to minus 50 DEG C, adding para-toluene sulfonate, performing temperature control stirring for 1 to 2 hours, then rising the temperature, stoppingrising the temperature when the temperature is risen to minus 35 to minus 30 DEG C, and performing temperature control stirring 8 to 9 hours, so as to obtain the racecadotril. The method has the advantages that the 2-benzyl-3-ethanethioyl crylic acid is taken as a starting material, triphosgene is taken as a halogenating reagent, and one-pot multi-step synthesis of the racecadotril is realized through accurate control on reaction temperature.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and in particular relates to a method for preparing racecadotril in one pot. Background technique [0002] Racecadotril is a neprilysin inhibitor, which was first developed by the French company Bioprojet and launched in France under the trade name of Tiorfan in 1993. It is mainly used to treat diarrhea in adults and children. In my country, racecadotril was listed as a recommended drug in the Chinese National Pediatric Diarrhea Treatment Consensus in 2011. [0003] US Patent No. 5,945,548 reports a synthetic route to racecadotril. In this route, racecadotril is prepared by condensation of 2-benzyl-3-thiolevulinic acid and benzyl glycine ester p-toluenesulfonate as raw materials through the condensation agent HOBT / DCC. [0004] [0005] Due to the use of DCC in this process, after the reaction of this substance is completed, it will become DCU which is difficult to remove in industria...

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 Applications(China)
IPC IPC(8): C07C327/32
CPCC07C327/32
Inventor 于康李宗涛张涛杨学谦刘印王孟孔令金王朋李芝菊高方美巩萍齐爱霞
Owner SHANDONG QIDU PHARMA
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com