Synthesis of non-steroidal anti-inflammatory drug—ketoprofen

Ketoprofen has significant analgesic and anti-inflammatory activities. It has been one of the most frequently used non-steroidal anti-inflammatory drugs in clinic for the treatment of inflammation and pain, and no cases of adverse side effects have been observed so far. To overcome the drawbacks of current synthetic methods, such as poor chemoselectivity and tedious work-up procedures, an optimization study was conducted. Using 3-iodobenzoic acid as a starting material, ketoprofen was prepared by Friedel-Crafts acylation with benzene, coupling reaction with diethyl malonate, methylation, Krapcho decarbalkoxylation and ester hydrolysis.The overall yield of the 5 synthetic steps is 58%. Compared with the reported methods, this optimized protocol has the advantages of mild reaction conditions, good chemoselectivity and facile operation. Thus, this protocol has a good prospect of industrial application.