Hydrochloric Acid → Gestodene

Participants

Reaction Steps

Acetylene is passed for about 45 minutes through a solution, cooled with ice water, of 100 ml. of n-butyllithium (approximately 15% strength in hexane) in 350 ml. of tetrahydrofuran. Thereafter, 10.0 g. of 18-methyl-3,3-(2',2'-dimethyl-1',3'-propylenedioxy)-5 and -5(10),15-estradien-17-one in 100 ml. of tetrahydrofuran is added dropwise thereto under agitation. After 30 minutes, the solution is combined with saturated ammonium chloride solution, diluted with ethyl acetate, washed neutral with water, and dried over sodium sulfate. The solution is concentrated to dryness under vacuum, thus obtaining 11.4 g. of crude 17α-ethynyl-18-methyl-3,3-(2',2'-dimethyl-1',3'-propylenedioxy)-5 and -5(10),15-estradien-17β-ol, which is suspended in 70 ml. of acetone. This reaction mixture is combined with 0.1 ml. of concentrated hydrochloric acid, stirred for 2 hours at room temperature, and then the solution is poured into ice water. The thus-precipitated product is vacuum-filtered, dissolved in ethyl acetate, and dried over sodium sulfate. After chromatographing the crude product on silica gel with 20% acetone-hexane, the product is 4.8 g. of 17α-ethynyl-17β-hydroxy-18-methyl-4,15-estradien-3-one, m.p. 199°-200°.

Provenance & Evidence