Preparing process of 5-propionyl-2-thiophenyl phenylacetate

Abstract

The process of preparing 5-propionyl-2-thiophenyl phenylacetate as the medicine intermediate oof zaltoprofen includes the following steps: Friedel-Crafts reaction of o-chloro phenylacetate and propionyl chloride in solvent to obtain 5-propionyl-2-chloro phenylacetic ester, hydrolysis of 5-propionyl-2-chloro phenylacetic ester in water solution of alkali metal hydroxide to produce 5-propionyl-2-chloro phenylacetate, the Ullmann condensation with thiophenol under the action of dehydrant and catalyst to obtain 5-propionyl-2-thiophenyl phenylacetic acid, and final esterification with alcohol to obtain 5-propionyl-2-thiophenyl phenylacetate. The present invention has the advantages of high yield, low cost, simple post-treatment and no environmental pollution, and is suitable for industrial production.

Description

Technical field [0001] The present invention relates to a preparation method of 5-propionyl-2-phenylthiophenyl acetate. 5-propionyl-2-phenylthiophenyl acetate is used to prepare "Zaltoprofen", namely A very important intermediate of 2-(10-oxo-10,1 dihydrodibenzo[b,f]thiazepine-2-yl)propionic acid. Background technique [0002] Zatorprofen is a powerful non-steroidal anti-inflammatory, analgesic and antipyretic drug. It selectively acts on the site of inflammation, but has no effect on other organs such as the stomach and kidneys. Compared with similar drugs such as naproxen and ibuprofen, it has the characteristics of high efficiency and less gastric side effects. Its structural formula is as follows: [0003] [0004] 5-Propionyl-2-phenylthiophenylacetate is currently a very important pharmaceutical intermediate for the preparation of zaltoprofen. Japanese Patent Publication No. 61-50061 and Publication No. 62-28085 Methyl chlorophenylacetate (10) is used as the raw material, ...

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Problems solved by technology

[0006] In the above two patent documents, since no solvent is used in the acylation reaction process, the mixing effect between the reactants is poor, which brings the disadvantages of incomplete reaction and low yield, and the separation of products is difficult, the post-treatment is complicated, and ice decomposition is required. After cooling, crystallization, suction filtration, water washing, recrystallization and other procedures, solid separation is very troublesome

In addition, in the reaction of preparing (13) from (11), the reaction conditions of water system and high temperature and high pressure are used, which is not suitable for industrial production; according to the preparation method provided by this patent document, many experiments are carried out, and the yield is very low

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