Short-step synthesis of naproxen. Regioselective Friedel-Crafts reaction of 2-chloro-2-alkylthio-propionates

Abstract 2-(6-Methoxy-2-naphthyl)propionic acid ( 4 ), dl-naproxen, was conveniently prepared by the regioselective reaction of alkyl 2-chloro-2-alkylthio-propionate ( 2 ) and 2-methoxynaphthalene ( 1 ) in good yield. This Friedel-Crafts reaction was found to be applicable to the other electron-rich aromatics.