Hydrochloric Acid → Gestodene

Participants

Reaction Steps

A 0.5 M solution of ethynylmagnesium bromide in THF (200 ml, 100 mmol) was added under a nitrogen atmosphere to a solution of 3-ethoxy-18-methyl-estra-3,5,15-trien-17-one (20 g, 64.1 mmol) in 2-MeTHF (40 ml) without exceeding 25° C. The mixture was stirred at room temperature for 2 h, cooled to 7° C. and EtOH (10 ml) was added. The mixture was stirred for 10 min, 3N aqueous hydrochloric acid solution was then added, and the mixture was stirred at a temperature below 10° C. for 2 h. The organic layer was separated and the aqueous layer was extracted with 2-MeTHF. The organic layers were combined and successively washed with 10% aqueous sodium chloride solution, 10% aqueous sodium hydrogencarbonate solution and 10% aqueous sodium chloride solution. 1-butanol (40 ml) was added to the organic layer and THF and 2-MeTHF were evaporated under vacuum at a temperature below 50° C. The remaining mixture in 1-butanol was cooled to 5° C. The precipitate was filtered, washed with water and dried under vacuum to afford crude 17α-ethynyl-17β-hydroxy-18-methyl-estra-4,15-dien-3-one (14.9 g, yield: 75%).

Provenance & Evidence