Preparation method of m-cyanomethyl methyl benzoate

Abstract

The invention discloses a preparation method of m-cyanomethyl methyl benzoate. According to the method, m-bromobenzoic acid is used as a starting raw material; the m-bromine methyl methyl benzoate is prepared through esterification; m-methoxy formyl phenethyl alcohol is obtained and prepared through Grignard reaction; through oxidization, the m-methoxy formyl phenylacetic acid is prepared; through amidation and dewatering, the m-cyanomethyl methyl benzoate is finally prepared. The preparation method provided by the invention has the advantages that the design is ingenious; the route is novel; the raw materials have low price and can be easily obtained; the process is simple; the implementation is easy; the yield is high; the purity of the obtained final product is high; the quality is high; no dangerous process exists; the extremely toxic substances of cyanides and expensive cyaniding reagents used in the conventional synthesis are avoided; the requirements on the equipment are simple; the production difficulty and the production cost investment are reduced; the industrial production can be favorably realized; the economic benefits are good.

Description

technical field [0001] The invention relates to the technical field of pharmacy, in particular to a method for preparing an intermediate of an antipyretic and analgesic drug ketoprofen, that is, a method for synthesizing methyl m-cyanomethylbenzoate. Background technique [0002] Ketoprofen, also known as ketoprofen, phenylketoprofen, Youbufen, Youprofen or Profenid, is chemically called α-methyl-3-benzoylphenylacetic acid, produced by the French company Rhone-Poulenc An excellent 2-arylpropionic acid non-steroidal anti-inflammatory analgesic drug developed by chemists Farge, Messer and Moutounier in 1967; its mechanism of action is mainly by inhibiting the biological activity of cyclooxygenase and lipoxygenase in the body, Thereby inhibiting the synthesis of prostaglandins and leukotrienes, which are prostaglandins and leukotrienes, which can resist the release of bradykinin, scavenge hydroxyl free radicals and stabilize lysosome membranes, thereby producing good antipyreti...

AI Technical Summary

Problems solved by technology

[0003] Methyl m-cyanomethylbenzoate is a key intermediate for the synthesis of ketoprofen. In the prior art, the synthesis of methyl m-cyanomethylbenzoate has the following schemes: scheme one, as disclosed in the patent No. US 20140275003 , prepared by coupling reaction of methyl m-bromobenzoate and 4-isoxazole boronic acid as raw materials, the yield of this route reaches 69%, but the used 4-isoxazole boronic acid and catalyst triphenylphosphine palladium chloride are relatively expensive; Scheme 2, as disclosed in Bioorganic & Medicinal Chemistry, 2013, 21, 2056-2067, WO 2012173784, is prepared using methyl m-bromomethylbenzoate as raw material and NaCN or potassium cyanide as raw material. The route is simple and the yield is high , but this route uses highly toxic substances sodium cyanide and potassium cyanide; Scheme 3: as disclosed in WO 2012006475, it is prepared from methyl m-bromomethylbenzoate and trimethylsilylnitrile. The yield of this scheme is It reaches 65%, but the cyanide reagent used in this route is more expensive, which limits the use; scheme four, as disclosed in WO 2000039125, is prepared from methyl m-bromomethylbenzoate and 2-methyl-2-hydroxypropionitrile , the reagents used in this scheme are more expensive; the schemes of the prior art either have low yields or are too high in production cost, or have relatively toxic reagents, and cannot be used in large-scale production. Therefore, it is urgent to develop a The new synthetic method of methyl m-cyanomethylbenzoate meets the production demand