Synthesis of Butibufen

Butibufen의 합성

A new method for the synthesis of butibufen, which is a non steroidal anti-iriflammatory agent, is described. Friedel-Crafts reaction of isobutylbenzene with ethyl $\alpha$-chloro-.alpha.-(methylthio) acetate (1) gives ethyl $\alpha$-methylthio-(p-isobutylphenyl)acetate (2). Ethyl 2-methylthio-2-(4-isobutylphenyl)butyrate (3) is obtained from treatment of the compound (2) with NaH and Etl. Butibufen (5) is synthesized by reductive desulfurization of the compound (3) with zinc dust-acetic acid or Raney nickel, followed by hydrolysis of the resultant ethyl 2-(4-isobutylphenyl)butyrate (4).