Ammonia → Oxendolone

Participants

Reaction Steps

These compounds can be prepared in a 10-stage process from 3-methoxy-1,3,5(10)-estratrien-17-one as starting material. In this process, 3-methoxy-1,3,5(10)-estratrien-17-one is enolized and acylated with acetic anhydride. The thus-obtained Δ16 -enol acetate is epoxidized with m-chloroperbenzoic acid and split in the presence of acetic acid. The resultant 16α-acetoxy-3-methoxy-1,3,5(10)-estratrien-17-one is saponified with sodium hydroxide solution in methanol and rearranged into 17β-hydroxy-3-methoxy-1,3,5(10)-estratrien-16-one. Subsequent Grignard reaction with ethylmagnesium iodide yields 3-methoxy-16,17β-dihydroxy-16α-ethyl-1,3,5(10)-estratriene, which is partially esterified with acetic anhydride/pyridine. The thus-obtained 3-methoxy-17β-acetoxy-16β-hydroxy-16α-ethyl-1,3,5(10)-estratriene is subjected to a Serini reaction with zinc/toulene and heating. The resultant 3-methoxy-16β-ethyl-1,3,5(10)-estratrien-17-one is reduced with sodium borohydride in ethanol. The ensuing 3-methoxy-16β-ethyl-1,3,5(10)-estratrien-17β-ol is reduced with lithium in liquid ammonia and then treated with hydrochloric acid/methanol, yielding the desired 17β-hydroxy-16β-ethyl-4-estren-3-one in a yield of barely 20% of theory.

Provenance & Evidence