Ammonia → (7alpha,17beta)-17-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]-7-ethyl-3-[(trimethylsilyl)oxy]estra-3,5-diene

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Reaction Conditions

Reaction Steps

i)—A mixture of lithium (0.647 g) and dry diethyl ether (26 ml) was cooled to −30° C. Bromoethane (3.45 ml) was added dropwise while maintaining the temperature below −25° C. After 30 min. stirring at −30° C. the solution of ethyllithium was added dropwise to a suspension of copper(I) iodide (4.0 g) in dry tetrahydrofuran (40 ml), cooled to −40° C. The resulting cuprate solution was stirred at −30° C. for 30 min. and a solution of (17β)-17-[[(1,1-dimethylethyl)dimethylsilyl]oxy]estra-4,6-dien-3-one [Nickisch, K. et al, Tetrahedron Lett. 29, 1533 (1988); 2.5 g] in dry tetrahydrofuran (20 ml) was added dropwise. Stirring was continued at −30° C. for 30 min., chlorotrimethylsilane (2.58 ml) was added and stirring was continued for another 30 min. The reaction mixture was poured into a mixture of a saturated aqueous solution of ammonium chloride and concentrated ammonia (9:1). The product was extracted into ethyl acetate; the combined organic phases were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine, dried over magnesium sulfate and concentrated under reduced pressure, to give (7α,17β)-17-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-7-ethyl-3-[(trimethylsilyl)oxy]estra-3,5-diene (2.81 g). The product was used in the following step without further purification.

Provenance & Evidence