Diethyl Ether → Gestodene

Participants

Reaction Steps

7.5 g. of magnesium filings is reacted in 140 ml. of tetrahydrofuran with 24 ml. of ethyl bromide to obtain ethylmagnesium bromide. To this Grignard solution is added 300 ml. of tetrahydrofuran, and under ice cooling acetylene is passed through the solution for about 40 minutes. Then, a solution of 5 g. of 18-methyl-3,3-(2',2'-dimethyl-1',3'-propanediol)-5-and -5(10),15-estradien-17-one in 200 ml. of tetrahydrofuran is added dropwise to the reaction solution, and the latter is agitated at room temperature. After 2 hours, the solution is carefully combined with an ammonium chloride solution and diluted with ether. The organic phase is washed repeatedly with water, dried over sodium sulfate, and evaporated to dryness under vacuum. After chromatographing the crude product on silica gel with 2.5-2.9% acetone-hexane, the yield is 3.1 g. of 17α-ethynyl-18-methyl-3,3-(2',2'-dimethyl-1',3'-propylenedioxy)-5,15 and -5(10),15-estradien-17β-ol; these compounds are agitated under reflux in 70 ml. of methanol and 14 ml. of water with 2.3 g. of oxalic acid for 40 minutes. The solution is diluted with ether, washed neutral with water, dried, and treated with activated carbon. After recrystallization from acetone-hexane, 1.4 g. of 17α-ethynyl-17β-hydroxy-18-methyl-4,15-estradien-3-one is obtained; m.p. 197.9°.

Provenance & Evidence