洛索洛芬钠的合成

Synthesis of Loxoprofen Sodium

苯乙腈经甲基化、水解和溴甲基化反应制得重要中间体2-(4-溴甲基苯基)丙酸(5),收率为53.2%,溴甲基化反应未见文献报道。5经甲酯化、缩合、水解和成钠盐得洛索洛芬钠,总收率40%(以苯乙腈计),纯度99.8%。该路线原料易得,操作简便,收率稳定,适合于工业化生产。

2-（4-Bromomethylphenyl）propionic acid（5）, the key intermediate of loxoprofen sodium, was synthesized from phenylacetonitrile by methylation, hydrolysis and bromomethylation with an overall yield of 53.2 %. The bromomethylation had not been found in literature. Loxoprofen sodium was obtained from 5 by esterification, condensation, hydrolyzation, and salt formation with an overall yield of 40 % （based on phenylacetonitrile） and a purity of 99.8 %. This process had the advantages of easily available starting materials, simple procedures, relatively steady yield, and was suitable for scale-up production.