SYNTHESES OF CARPROFEN, A CARBAZOLE-BASED NONSTEROIDAL ANTIINFLAMMATORY AGENT

Syntheses of carprofen (6) have been achieved by two approaches from c arbazole (11). In one, 2,9-diacetylcarbazole (12) and 2-acetylcarbazol e (13) were chlorinated with trichloroisocyanuric acid (15) to give th e 6-chloro derivatives (16) and (17), respectively. Reduction of 16 wi th NaBH4, followed by acetylation, cyanide displacement, and hydrolysi s afforded 6 in 73% yield from 16. Alternatively, 17 was converted int o its trimethylsilyloxy cyanohydrin derivative (27), which was reduced with SnCl2 and hydrolysed to give 6 in 75% yield from 17. In the othe r approach, the ketone (18), derived by a Friedel-Crafts acylation of 9-acetylcarbazole with 2-chloropropanoyl chloride followed by chlorina tion with 15, was converted into the hydroxyketal (28) with methanolic NaOMe. Mesylation of 28, followed by a modified Favorskii rearrangeme nt and hydrolysis gave 6 in 73% yield from 18.