Trifluoroacetic acid → Trifluoroacetic anhydride

Participants

Reaction Steps

Epoxidation of the 21-methoxy compound (7) with hexafluoroacetone trihydrate and 30% hydrogen peroxide produce a 2:1 mixture of 5α,10α- and 5β,10β-epoxides (8) as evidenced by NMR. As attempts to isolate pure 5α,10α-epoxide (8) were unsuccessful, the crude mixture was used directly on to the copper (I) catalyzed Grignard reaction, to obtain the 11β-[4-(N,N-dimethylamino)phenyl] derivative (9). Hydrolysis with trifluoroacetic acid restored the 4,9-diene-3,20-dione structure (10). Acetylation of the 17α-hydroxy compound (10) with the mixed anhydride formed from trifluoroacetic anhydride and acetic acid afforded the desired 19-norprogesterone compound (11).

Provenance & Evidence