Method for preparing 4-felbinac through rearrangement reaction

A felbinac and rearrangement reaction technology, which is applied in the field of pharmaceutical chemical synthesis, can solve the problems of low yield, difficult industrialization, difficult removal of impurities, high toxicity, etc., and achieve the effects of easy industrial production, simple operation, and low toxicity

Inactive Publication Date: 2012-06-20
SHANGHAI TUPA MEDICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] In addition, there will be some other synthetic routes, but almost all of them have these or those deficiencies: either the impurities are difficult to remove, or the yield is low and industrialization is diffic

Method used

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  • Method for preparing 4-felbinac through rearrangement reaction
  • Method for preparing 4-felbinac through rearrangement reaction

Examples

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Effect test

Embodiment 1

[0046] A method utilizing rearrangement reaction to prepare 4-biphenylacetic acid, the steps comprising:

[0047] (1) Preparation of 4-phenyl-a-chloroacetophenone by Friedel-Crafts acylation reaction

[0048] Dissolve 30.8 grams of biphenyl (0.2moL) and 24.6 grams of chloroacetyl chloride (0.22moL) in 50mL of dichloromethane, and add them to the dropping funnel for later use; meanwhile, add 32 grams of aluminum trichloride (0.24mol) and 150mL Add dichloromethane into the three-necked flask with mechanical stirring, and cool it to below 0°C under rapid stirring, then drop the mixture of biphenyl and chloroacetyl chloride in the dropping funnel into the three-necked flask, Complete the addition within 2 hours, continue to stir at below 0°C for 1 hour, and detect with gas chromatography until the biphenyl content is less than 1%;

[0049] After the reaction is complete, pour the reaction solution into 200 g of ice water and stir rapidly to complete the hydrolysis; several layers...

Embodiment 2

[0059] A method utilizing rearrangement reaction to prepare 4-biphenylacetic acid, the steps comprising:

[0060] (1) Preparation of 4-phenyl-a-chloroacetophenone by Friedel-Crafts acylation reaction

[0061] Dissolve 92.4 grams of biphenyl (0.6moL) and 73.8 grams of chloroacetyl chloride (0.66moL) in 100mL of dichloromethane, and add to the dropping funnel for later use; at the same time, 96 grams of aluminum trichloride (0.72mol) and 250mL Add dichloromethane into a three-necked flask with mechanical stirring, and cool it to below -10°C under rapid stirring, then drop the mixture of biphenyl and chloroacetyl chloride in the dropping funnel into the three-necked flask, Add within 2 hours, continue to stir at -10°C for 2 hours, and detect with gas chromatography until the biphenyl content is less than 1%;

[0062] After the reaction is complete, pour the reaction liquid into 400 grams of ice water, and stir rapidly to complete the hydrolysis; separate and collect several laye...

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Abstract

The invention relates to a medicinal chemistry synthesis technology, in particular to a method for preparing 4-felbinac through rearrangement reaction. The method comprises the following steps of: 1, performing Friedel-Crafts acylation on biphenyl and chloroacetyl chloride which serve as raw materials by using chloroform, dichloromethane or 1,2-dichloroethane as a solvent and alchlor as a catalyst to obtain 4-phenyl-alpha-chloroacetophenone; 2, performing condensation on the 4-phenyl-alpha-chloroacetophenon and neopentyl glycol under the catalysis of toluenesulfonic acid to prepare ketal; 3, performing hydrolysis and acidification through the rearrangement reaction to obtain coarse 4-felbinac; and 4, recrystallizing the coarse 4-felbinac by using ethanol, ethyl acetate or 40 to 70 percent acetic acid to obtain the 4-felbinac with the purity of 99.8 percent. The method has the advantages that: the raw materials are readily available and low in toxicity, and new compounds with high toxicity cannot be generated in production; and conventional equipment is used, the yield of the coarse product is 70 to 80 percent and the prepared 4-felbinac has the purity of 99.8 percent.

Description

technical field [0001] The invention relates to the field of medical chemical synthesis technology, in particular to a preparation method of non-steroidal anti-inflammatory drug 4-felbinac. Background technique [0002] Felbinac gel (Napagaln) is a non-steroidal anti-inflammatory drug whose main active ingredient is 4-felbinac. The 3% felbinac gel was developed by Ledede Corporation of Japan, and was first listed in Japan in 1986 under the trade name Napageln. Later, 3% felbinac gel was launched in the UK under the trade name "Traxamgel". At present, the drug has been launched in more than a dozen countries including the United Kingdom, the Philippines, Germany, South Korea, Belgium and Denmark. Felbinac gel is mainly used for the treatment of osteoarthritis, frozen shoulder, tenosynovitis, peritendinitis, muscle pain, trauma swelling, trauma pain and other symptoms. [0003] In addition, 4-felbinac is also an active metabolite of the anti-inflammatory and analgesic drug ...

Claims

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Application Information

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IPC IPC(8): C07C57/38C07C27/02C07C51/43
Inventor 褚长虎赵谦
Owner SHANGHAI TUPA MEDICAL TECH
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