Potassium Hydroxide → 18,18-Difluoro-androst-4-ene-3,17-dione

Participants

Reaction Steps

After adding 22 ml of a 10% strength potassium hydroxide solution, a solution of 2.3 g of 18,18-difluoro-androst-5-ene-3β,17β-diol diacetate (crude product) in 130 ml of methanol is stirred for 1 hour at room temperature, whilst passing nitrogen through the solution. The reaction mixture is then concentrated to about 60 ml in an aspirator vacuum and taken up in ethyl acetate and the mixture is washed with 1 N hydrochloric acid and with water until neutral, dried and evaporated in an aspirator vacuum. The crude 18,18-difluoro-androst-5-ene-3β,17β-diol is suspended, without purification, in 80 ml of toluene, the suspension is treated with 8 ml of cyclohexanone and 2.2 g of aluminium isopropylate and the mixture is refluxed for 45 minutes with stirring. The cooled reaction mixture is worked up by diluting it with ethyl acetate and washing it successively with saturated Seignette salt solution (potassium sodium tartrate solution) and with water. The washings are further extracted with ethyl acetate and the organic phases are dried and evaporated in an aspirator vacuum. The amorphous residue is then chromatographed over 100 times the amount by weight of silica gel. Elution with a mixture of hexane/ethyl acetate (3:1) gives successively, in approximately equal amounts by weight, 18,18-difluoro-androst-4-ene-3,17-dione, which after recrystallisation from acetone/hexane melts at 161°-163° C, and 18,18-difluoro-17β-hydroxy-androst-4-en-3-one of melting point 183°-184° C (recrystallised from acetone/hexane).

Provenance & Evidence