Study On The Process For The Synthesis Of Loxoprofen Sodium

Loxoprofen sodium is a new kind of anti-inflammatory drugs,which belongs to arylpropionic acid derivatives.In 1986,Loxoprofen sodium is developed by Sankyo Pharmaceutical Company of Japan,which has many advantages such as small oral dosage,high efficiency,less side-effects.It has been widely used in clinical therapy.The synthetic route of loxoprofen sodium has been reported by many literatures,which involved the key intermediate 2-(4-halo-methylphenyl)propionic acid or its ester.In this thesis,we designed a new synthetic process to prepare loxoprofen sodium starting from benzene as raw material,followed by Friedel-Crafts acylation,chlorination,ketal rearrangement,hydrolysis,esterification and chloromethylation to give methyl 2(4-chloromethylphenyl)propanoate,followed by condensation with 2-ethoxycarbonyl-cyclopentanone and decarboxylation to provide loxoprofen acid.Furthermore,the key step is the synthesis of methyl 2(4-chloromethylphenyl)propionate.The conditions of chloromethylation were investigated and optimized systematically.The new synthetic route to the synthesis of loxoprofen sodium has been developed.This synthetic route has some advantages such as cheap and readily available raw materials,simple operation and high yield,which is feasible to a large-scale preparation.