- Syntheses of Carprofen, A Carbazole-Based Nonsteroidal Anti-Inflammatory Agent
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Syntheses of carprofen (6) have been achieved by two approaches from carbazole (11).In one, 2,9-diacetylcarbazole (12) and 2-acetylcarbazole (13) were chlorinated with trichloroisocyanuric acid (15) to give the 6-chloro derivatives (16) and (17), respectively.Reduction of 16 with NaBH4, followed by acetylation, cyanide displacement, and hydrolysis afforded 6 in 73percent yield from 16.Alternatively, 17 was converted into its trimethylsilyloxy cyanohydrin derivative (27), which was reduced with SnCl2 and hydrolysed to give 6 in 75percent yield from 17.In the other approach, the ketone (18), derived by a Friedel-Crafts acylation of 9-acetylcarbazole with 2-chloropropanoyl chloride followed by chlorination with 15, was converted into the hydroxyketal (28) with methanolic NaOMe.Mesylation of 28, followed by a modified Favorskii rearrangement and hydrolysis gave 6 in 73percent yield from 18.
- Manchand, Percy S.,Coffen, David L.,Belica, Peter S.,Wong, Frederick,Wong, Harry S.,Berger, Leo
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p. 833 - 846
(2007/10/02)
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