An alternative synthesis of 17β‐hydroxy‐7α‐methyl‐19‐nor‐17α‐pregn‐5(10)‐en‐20‐yn‐3‐one (Org OD 14)

Abstract

Abstract The title compound ( 4 ) was prepared starting from 17β,19‐dihydroxyandrosta‐4,6‐dien‐3‐one 17,19‐diacetate ( 5 ). Copper‐catalyzed conjugate addition of methylmagnesium iodide gave, after hydrolysis, 17β,19‐dihydroxy‐7α‐methylandrost‐4‐en‐3‐one ( 8a ), which was converted by oxidation and deacylation into 7α‐methylestr‐5(10)‐ene‐3,17‐dione ( 11 ). Selective protection of the 3‐keto group as the dimethyl acetal, followed by ethynylation and deacetalization, gave the desired product 4. The 7β‐methyl adduct, a by‐product in the Grignard reaction, was removed after the oxidation step. Its structure was confirmed by an independent synthesis of the 7β‐methyl‐19‐aldehyde 9b.