1-[difluoromethyl(ethoxy)phosphoryl]oxyethane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.4 g of diethyl-(difluoromethyl)-phosphonate in 150 ml of tetrahydrofuran is slowly mixed with 25 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 6 g of 3-methoxy-18-methyl-estra-1,3,5(10)-trien-17-one in 173 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 6 hours. For working-up, it is diluted 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. 5.4 g of 17-difluoromethylene-3-methoxy-18-methyl-estra-1,3,5(10)-triene is obtained as colorless crystals with a melting point of 145-146° C., [α]D22 =+40.2° (c=0.515% in pyridine). stirred for 15 minutes slowly heated at a bath temperature of from -50° C. to 100° C. refluxed for 6 hours washed with water as well as with saturated sodium chloride solution dried on sodium sulfate concentrated by evaporation in a vacuum chromatographed on silica gel with hexane/ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.4 g of diethyl-(difluoromethyl)-phosphonate in 150 ml of tetrahydrofuran is slowly mixed with 25 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 5.6 g of 3-methoxy-estra-1,3,5(10),15-tetraen-17-one in 173 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 6 hours. For working-up, half the volume is concentrated by evaporation in a vacuum, diluted 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. 3.0 g of 17-difluoromethylene-3-methoxy-estra-1,3,5(10),15-tetraene is obtained as colorless crystals with a melting point of 122-123° C., [α]D22 =-120.9° (c=0.515% in pyridine). stirred for 15 minutes slowly heated at a bath temperature of from -50° C. to 100° C. refluxed for 6 hours half the volume is concentrated by evaporation in a vacuum diluted with ethyl acetate washed with water as well as with saturated sodium chloride solution dried on sodium sulfate concentrated by evaporation in a vacuum chromatographed on silica gel with hexane/ethyl acetate/triethylamine

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.4 g of diethyl-(difluoromethyl)-phosphonate in 150 ml of tetrahydrofuran is slowly mixed with 25 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 6 g of 3-methoxy-18-methyl-estra-1,3,5(10)-trien-17-one in 173 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 6 hours. For working-up, it is diluted 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. 5.4 g of 17-difluoromethylene-3-methoxy-18-methyl-estra -1,3,5(10)-triene is obtained as colorless crystals with a melting point of 145-146° C., [α]D22 =+40.2° (c=0.515% in pyridine). stirred for 15 minutes slowly heated at a bath temperature of from -50° C. to 100° C. refluxed for 6 hours washed with water as well as with saturated sodium chloride solution dried on sodium sulfate concentrated by evaporation in a vacuum chromatographed on silica gel with hexane/ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.4 g of diethyl-(difluoromethyl)-phosphonate in 150 ml of tetrahydrofuran is slowly mixed with 25 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 5.6 g of 3-methoxy-estra-1,3,5(10),15-tetraen-17-one in 173 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 6 hours. For working-up, half the volume is concentrated by evaporation in a vacuum, diluted 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. 3.0 g of 17-difluoromethylene-3-methoxy-estra -1,3,5(10),15-tetraene is obtained as colorless crystals with a melting point of 122-123° C., [α]D22 -120.9° (c=0.515% in pyridine). stirred for 15 minutes slowly heated at a bath temperature of from -50° C. to 100° C. refluxed for 6 hours half the volume is concentrated by evaporation in a vacuum diluted with ethyl acetate washed with water as well as with saturated sodium chloride solution dried on sodium sulfate concentrated by evaporation in a vacuum chromatographed on silica gel with hexane/ethyl acetate/triethylamine

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.4 g of diethyl-(difluoromethyl)-phosphonate in 150 ml of tetrahydrofuran is slowly mixed with 25 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 5.6 g of 3-methoxy-estra-1,3,5(10),15-tetraen-17-one in 173 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 6 hours. For working-up, half the volume is concentrated by evaporation in a vacuum, diluted 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. 3.0 g of 17-difluoromethylene-3-methoxy-estra -1,3,5(10),15-tetraene is obtained as colorless crystals with a melting point of 122-123° C., [α]D22 -120.9° (c=0.515% in pyridine). stirred for 15 minutes slowly heated at a bath temperature of from -50° C. to 100° C. refluxed for 6 hours half the volume is concentrated by evaporation in a vacuum diluted with ethyl acetate washed with water as well as with saturated sodium chloride solution dried on sodium sulfate concentrated by evaporation in a vacuum chromatographed on silica gel with hexane/ethyl acetate/triethylamine

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of diethyl difluoromethanephosphonate (1.0 g, 5.316 mmol) in THF (50 mL) 2 M LDA (626 mg, 5.847 mmol) was added at −78° C. and stirred for 30 min. Tetradecyl bromide (1.474 g, 5.316 mmol) in THF (10 mL) was added to the mixture at −78° C. and the reaction mixture was stirred overnight. THF was evaporated and the residual oil was purified by flash chromatography using 30% ethyl acetate in hexane as eluent to give 817 mg (40%) of compound 10 as colorless oil. 1H NMR (CDCl3): δ4.26 (m, 4H), 2.05 (m, 2H), 1.56 (m, 2H), 1.37 (t, J=6.9 Hz, 6H), 1.25 (br s, 22H), 0.87 (t, J=6.6 Hz, 3H); MS: [M+23Na] at m/z 407.2. the reaction mixture was stirred overnight THF was evaporated the residual oil was purified by flash chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.4 g of diethyl-(difluoromethyl)-phosphonate in 150 ml of tetrahydrofuran is slowly mixed with 25 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 6 g of 3-methoxy-18-methyl-estra-1,3,5(10)-trien-17-one in 173 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 6 hours. For working-up, it is diluted 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. 5.4 g of 17-difluoromethylene-3-methoxy-18-methyl-estra-1,3,5(10)-triene is obtained as colorless crystals with a melting point of 145-146° C., [α]D22 =+40.2° (c=0.515% in pyridine). stirred for 15 minutes slowly heated at a bath temperature of from -50° C. to 100° C. refluxed for 6 hours washed with water as well as with saturated sodium chloride solution dried on sodium sulfate concentrated by evaporation in a vacuum chromatographed on silica gel with hexane/ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.4 g of diethyl-(difluoromethyl)-phosphonate in 150 ml of tetrahydrofuran is slowly mixed with 25 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 6 g of 3-methoxy-18-methyl-estra-1,3,5(10)-trien-17-one in 173 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 6 hours. For working-up, it is diluted 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. 5.4 g of 17-difluoromethylene-3-methoxy-18-methyl-estra-1,3,5(10)-triene is obtained as colorless crystals with a melting point of 145-146° C., [α]D22 =+40.2° (c=0.515% in pyridine). stirred for 15 minutes slowly heated at a bath temperature of from -50° C. to 100° C. refluxed for 6 hours washed with water as well as with saturated sodium chloride solution dried on sodium sulfate concentrated by evaporation in a vacuum chromatographed on silica gel with hexane/ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.4 g of diethyl-(difluoromethyl)-phosphonate in 150 ml of tetrahydrofuran is slowly mixed with 25 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 5.6 g of 3-methoxy-estra-1,3,5(10),15-tetraen-17-one in 173 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 6 hours. For working-up, half the volume is concentrated by evaporation in a vacuum, diluted 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. 3.0 g of 17-difluoromethylene-3-methoxy-estra-1,3,5(10),15-tetraene is obtained as colorless crystals with a melting point of 122-123° C., [α]D22 =-120.9° (c=0.515% in pyridine). stirred for 15 minutes slowly heated at a bath temperature of from -50° C. to 100° C. refluxed for 6 hours half the volume is concentrated by evaporation in a vacuum diluted with ethyl acetate washed with water as well as with saturated sodium chloride solution dried on sodium sulfate concentrated by evaporation in a vacuum chromatographed on silica gel with hexane/ethyl acetate/triethylamine

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.4 g of diethyl-(difluoromethyl)-phosphonate in 150 ml of tetrahydrofuran is slowly mixed with 25 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 5.6 g of 3-methoxy-estra-1,3,5(10),15-tetraen-17-one in 173 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 6 hours. For working-up, half the volume is concentrated by evaporation in a vacuum, diluted 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. 3.0 g of 17-difluoromethylene-3-methoxy-estra-1,3,5(10),15-tetraene is obtained as colorless crystals with a melting point of 122-123° C., [α]D22 =-120.9° (c=0.515% in pyridine). stirred for 15 minutes slowly heated at a bath temperature of from -50° C. to 100° C. refluxed for 6 hours half the volume is concentrated by evaporation in a vacuum diluted with ethyl acetate washed with water as well as with saturated sodium chloride solution dried on sodium sulfate concentrated by evaporation in a vacuum chromatographed on silica gel with hexane/ethyl acetate/triethylamine

反応条件: temp:0.00; pressure:0.00; stir: