Preparation method of racecadotril

A technology for racecadotril and benzyl glycine, which is applied in the field of monothiocarboxylic acid, can solve the problems of high product impurity content, high price and high production cost of racecadotril, and achieves high yield and reaction process. short effect

A technology for racecadotril and benzyl glycine, which is applied in the field of monothiocarboxylic acid, can solve the problems of high product impurity content, high price and high production cost of racecadotril, and achieves high yield and reaction process. short effect

CN101768095AInactive Publication Date: 2010-07-07SHANDONG QIDU PHARMA
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  • Preparation method of racecadotril
  • Preparation method of racecadotril
  • Preparation method of racecadotril

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027]

[0028] 1) Preparation of 2-benzyl-3-thioacetylpropionyl chloride

[0029] A 500ml three-necked reaction flask with a condensing tube is equipped with a tail gas absorption device, and 72g (0.3mol) of 2-benzyl-3-thioacetylpropionic acid, 57.1g (0.48mol) of thionyl chloride, and 300ml of toluene are added, slowly The temperature was raised to 35°C for 1 hour, and then the temperature was slowly raised to 70°C to continue the reaction for 3 hours. After the reaction was complete, 76.5 g of a light yellow oily substance was evaporated to dryness under reduced pressure.

[0030]

[0031] 2) Preparation of racecadotril

[0032] Add 860ml of dichloromethane and 101.1g (0.3mol) of benzyl glycine ester p-toluenesulfonate to a 2000ml three-necked flask, cool down in an ice bath to 0-5°C, add 125ml of triethylamine under stirring, after the addition is complete, add dropwise 76.5 g of 2-benzyl-3-thioacetylpropionyl chloride was prepared. After the dropwise reaction was c...

Embodiment 2

[0034]

[0035] 1) Preparation of 2-benzyl-3-thioacetylpropionyl chloride

[0036] A 500ml three-necked reaction flask with a condensing tube was installed with a tail gas absorption device, and 72g (0.3mol) of 2-benzyl-3-thioacetylpropionic acid, 38.1g (0.3mol) of oxalyl chloride, and 300ml of toluene were added, and the temperature was slowly raised to React at 35°C for 1 hour, then slowly raise the temperature to 60°C and continue to react for 3 hours. After the reaction is complete, the solvent is evaporated to dryness under reduced pressure to obtain 75.9 g of a light yellow oil.

[0037]

[0038] 2) Preparation of racecadotril

[0039] Add 860ml of dichloromethane and 101.1g (0.3mol) of benzyl glycine ester p-toluenesulfonate to a 2000ml three-necked flask, cool down in an ice bath to 0-5°C, add 124.2g of potassium carbonate while stirring, after the addition is complete, add step 1 dropwise ) 75.9 g of 2-benzyl-3-thioacetylpropionyl chloride prepared. After the ...

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Abstract

The invention relates to a preparation method of racemic N-[2-acetyl mercapto) methyl]-1-oxygen-3-phenyl propyl] glycine benzyl ester (racecadotril), which is essentially prepared by amidation reaction of 2-benzyl-3-thio-acetyl propionyl halide and glycine benzyl ester salt or glycine benzyl ester. Compared with the prior art, the invention has short reaction process, high yield. The prepared racecadotril is mainly used for the treatment of acute diarrhea for adults and children.

Description

technical field [0001] The invention belongs to the technical field of thiocarboxylic acid, specifically a racemic N-[2-acetylmercapto)methyl]-1-oxygen-3-phenylpropyl]glycine benzyl ester (racecadotril) . The racecadotril of the present invention is mainly used for treating acute diarrhea in adults or children. Background technique [0002] Racecadotril (Racecadotril), chemical name: (R.S) N-[2-acetylthio)methyl]-1-oxo-3-phenylpropyl]glycine benzyl ester, is a drug for treating acute diarrhea , for the treatment of acute diarrhea in adults or children. [0003] In the synthetic route of racecadotril reported in U.S. Patent No. 5,945,548, 2-benzyl-3-thioacetylpropionic acid and glycine benzyl ester p-toluenesulfonate are prepared by condensation of condensing agent DCC and HOBT in tetrahydrofuran . [0004] [0005] Since the by-product DCU is produced in the preparation process, DCU is difficult to completely remove in the industrial production process, resulting in e...

Claims

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Application Information

Patent Timeline
07 Jul 2010
Publication
CN101768095A
IPC
C07C327/22; A61P1/12
Inventors
丁燕军; 冯波