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Method for preparing loxoprofen intermediate

An intermediate and system technology, applied in the field of preparation of loxoprofen intermediates, can solve the problems of poor product selectivity, low conversion rate, many by-products, etc., and achieve low production cost, high conversion rate, and few by-products. Effect

Inactive Publication Date: 2016-07-13
UPCHEM CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] The purpose of this invention is to provide a kind of preparation method of loxoprofen intermediate, solve existing loxoprofen intermediate preparation method, product selectivity is poor, purity is low, conversion rate is low, by product is many, raw material is expensive, and cost is high The problem

Method used

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  • Method for preparing loxoprofen intermediate
  • Method for preparing loxoprofen intermediate
  • Method for preparing loxoprofen intermediate

Examples

Experimental program
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Effect test

Embodiment 1

[0070] The present embodiment loxoprofen intermediate preparation method, concrete steps are as follows:

[0071] 1) Preparation stage of 2-(phenylcyano)sodium propionate

[0072] Add 10g, 10g, 5.0g, and 45g of phenylacetonitrile, DMC, sodium methoxide, and toluene into the drying reactor, stir and heat up to 60°C, and keep the temperature for 1 hour; The product methanol was distilled off until no methanol was left, and the reaction solution was sampled and tested for later use.

[0073] 2) Preparation stage of methyl 2-(phenylcyano)propionate

[0074] Lower the temperature of the upper reaction solution to 35°C, control the reaction temperature at 35°C and add 14g of DMS dropwise at a constant speed. water, stirred, dissolved and separated into layers, and the toluene was recovered by distillation under reduced pressure until no toluene was evaporated to obtain methyl 2-(phenylcyano)propionate;

[0075] 3) 2-phenylpropionitrile preparation stage

[0076] 12g of 30% liqui...

Embodiment 2

[0082] The present embodiment loxoprofen intermediate preparation method, concrete steps are as follows:

[0083] 1) Preparation stage of 2-(phenylcyano)sodium propionate

[0084] Add 10g, 15g, 6.0g, and 50g of phenylacetonitrile, DMC, sodium methoxide, and toluene into the drying reactor, stir and heat up to 100°C, and keep warm for 5.5 hours; The product methanol was distilled off until no methanol was left, and the reaction solution was sampled and tested for later use.

[0085] 2) Preparation stage of methyl 2-(phenylcyano)propionate

[0086] Lower the temperature of the upper reaction solution to 35°C, control the reaction temperature at 85°C and add 10g of DMS dropwise at a constant speed. water, stirred, dissolved and separated into layers, and the toluene was recovered by distillation under reduced pressure until no toluene was evaporated to obtain methyl 2-(phenylcyano)propionate;

[0087] 3) 2-phenylpropionitrile preparation stage

[0088] Mix 11g of 30% liquid c...

Embodiment 3

[0094] The present embodiment loxoprofen intermediate preparation method, concrete steps are as follows:

[0095] 1) Preparation stage of 2-(phenylcyano)sodium propionate

[0096] Add phenylacetonitrile, DMC, a mixture of sodium methoxide and methanol (the content of sodium methoxide is 30%), and toluene respectively 10g, 12.5g, 18.33g, and 47.5g into the drying reactor, stir and heat up to 20°C, and keep warm for 10 Hours; after the reaction, the by-product methanol was distilled at 80°C under normal pressure until no methanol was distilled out, and the reaction solution was sampled and tested for use.

[0097] 2) Preparation stage of methyl 2-(phenylcyano)propionate

[0098] Lower the temperature of the upper reaction solution to 35°C, control the reaction temperature at 60°C and add 10g of DMS dropwise at a constant speed. water, stirred, dissolved and separated into layers, and the toluene was recovered by distillation under reduced pressure until no toluene was evaporat...

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Abstract

A method for preparing a loxoprofen intermediate comprises the following steps that 1, on the presence of sodium alkoxide, benzyl cyanide and dimethyl carbonate are subjected to methylation in an organic solvent, and 2-(phenyl cyano) sodium propionate is obtained; 2, 2-(phenyl cyano) sodium propionate and dimethyl sulfate react in an organic solvent to obtain 2-(phenyl cyano) methyl propionate; 4, 2-(phenyl cyano) methyl propionate reacts under the alkaline condition to obtain 2-phenyl propionitrile; 4, 2-phenyl propionitrile is hydrolyzed under the alkaline condition, acid is added for acidizing after the reaction to obtain 2-phenylpropionic acid; 5, 2-phenylpropionic acid, hydrobromic acid and paraformaldehyde are mixed and subjected to a bromine methylation reaction under the acidic condition, and 2-(4-tribromomethyl phenyl) propionic acid is obtained.According to the method, a new synthesis route is designed, product selectivity is good, the purity is high, the conversion rate is high, and few by-products are generated; the raw materials are simple and easy to obtain, the production conditions are mild, the process is simple, production cost is low, and pollution is small.

Description

technical field [0001] The invention relates to the field of synthesis of pharmaceutical intermediates, in particular to a preparation method of a loxoprofen intermediate. Background technique [0002] Loxoprofen (Loxoprofen Sodium) belongs to the new type of non-steroidal anti-inflammatory drugs of aryl propionic acid, which has the advantages of small oral dose, high efficiency, and small side effects. 2-(4-Bromomethylphenyl)propionic acid is one of the key intermediates for the synthesis of loxoprofen, and it has been clinically shown to have the best analgesic, anti-inflammatory and anti-rheumatic effects among known aryl propionic acid drugs. Good, so it is favored by experts and scholars at home and abroad, as well as respected by the medical profession and patients. This product was developed and launched by Sankyo Pharmaceutical Co., Ltd. in Japan in 1986. It has been launched in Japan, South Korea, Europe, America and many other countries, with a strong growth mome...

Claims

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Application Information

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IPC IPC(8): C07C51/363C07C57/58C07C253/30C07C255/41C07C255/33C07C51/08C07C57/30
CPCC07C253/30C07C51/08C07C51/363
Inventor 夏晨东傅华伟陈国全
Owner UPCHEM CHINA
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