Synthesis of the COX-2 Inhibitor GW406381X

Significance

A new metal- and halogen-free variant of the Friedel-Crafts acylation using carboxylic acid substrates is promoted by methanesulfonic anhydride (1.3 equivalent) and as little as 1.3 equivalent of the arene. In general, no additional solvent is required making the reaction very atom-efficient. The methanesulfonic acid waste stream is biodegradable.