反应详情

A solution of 3 g of difluoromethyldiphenylphosphine oxide in 85 ml of tetrahydrofuran is slowly mixed with 6 ml of 2 M lithium diisopropylamide solution at a bath temperature of -50° C., and it is stirred for 1 hour. Then, a solution of 1.7 g of 3-tetrahydropyranyloxy-estra-1,3,5(10),7-tetraen-17-one in 42 ml of tetrahydrofuran is slowly added, stirred for 15 minutes, slowly heated at a bath temperature of from -50° C. to 100° C. and refluxed for 2.5 hours. For working-up, it is diluted with ethyl acetate and water, suctioned off on Celite, rewashed with ethyl acetate, washed with water as well as with saturated sodium chloride solution, dried on sodium sulfate, concentrated by evaporation in a vacuum and chromatographed on silica gel with hexane/ethyl acetate/triethylamine. 1.0 g of 17-difluoromethylene-3-tetrahydropyranyloxy-estra-1,3,5(10),7-tetraene is obtained as colorless crystals with a melting point of 83-84° C., [α]D 22 =+139.6° (c=0.5% in pyridine).

1. stirringstirred for 15 minutes
2. temperatureslowly heated at a bath temperature of from -50° C. to 100° C.
3. temperaturerefluxed for 2.5 hours
4. washwashed with water as well as with saturated sodium chloride solution
5. customdried on sodium sulfate
6. concentrationconcentrated by evaporation in a vacuum
7. customchromatographed on silica gel with hexane/ethyl acetate/triethylamine