Efficient syntheses of 2-(3′,5′-difluorophenyl)-3-(4′-methylsulfonylphenyl)cyclopent-2-enone, a potent COX-2 inhibitor

Abstract 2-(3′,5′-Difluorophenyl)-3-(4′-methylsulfonylphenyl)cyclopent-2-enone ( 1 ) displays high selectivity and potency against COX-2. Three efficient syntheses of this diarylcyclopentenone are described. The first approach employs a Suzuki coupling reaction as the key step while the second synthesis features an intramolecular Friedel-Crafts acylation. The third, and preferred route to this compound involves a sequential malonate alkylation and acylation and ring-closure sequence.