Method for preparing 4-felbinac through rearrangement reaction

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 ...

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 difficult, or the raw materials are expensive and difficult to obtain, or it is necessary to Using highly toxic raw materials, they are harmful to the environment, so they are hardly suitable for industrial scale production

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