A convenient synthesis of the key intermediate of selective COX-2 inhibitor Etoricoxib

Abstract

An original strategy for the synthesis of ketone 1, the key intermediate for preparing Etoricoxib, an important nonsteroidal anti-inflammatory drug, has been developed. Inexpensive 5-hydroxy-2-methylpyridine was converted to the corresponding acetyl derivative in four practical synthetic steps. The following palladium-catalyzed α-arylation of acetylpicoline with 4-bromo- or 4-chlorophenyl methyl sulfone was efficiently optimized in order to afford ketone 1 in remarkable yield.