benzyl (3S)-3-fluoropyrrolidine-1-carboxylate

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

実験手順: A stirred mixture of 20.85 g (0.360 moles) of potassium fluoride spray-dried and 18.0 g (0.048 moles) of (3R)-N- benzyloxycarbonyl-3-hydroxypyrrolidine in 160 ml of freshly distilled ethylene glycol was kept at 85° C. for 15 h under nitrogen atmosphere. spray-dried

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 5-L, 3-neck, round bottom flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen bubbler was charged with 375 mL (2.84 mol) of (diethylamino)sulfur trifluoride and 400 mL of dichloromethane. The solution was cooled to −78° C. To this was added via addition funnel a solution of 304 g (1.37 mol) of benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate in 400 mL of dichloromethane over a 2-h period keeping the reaction temperature below −70° C. The reaction mixture was allowed to stir and warm slowly to ambient temperature overnight. The reaction mixture was added portion-wise with caution to a large extractor containing ice, water, and saturated aqueous sodium bicarbonate solution. The mixture was extracted with 8 L of ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated to give a brown oil. Purification by flash chromatography (silica gel, eluting with a 10 to 30% ethyl acetate/hexane gradient) gave the title compound as a brown oil. thermocouple, addition funnel the reaction temperature below −70° C warm slowly to ambient temperature overnight The reaction mixture was added portion-wise with caution to a large extractor The mixture was extracted with 8 L of ethyl acetate The organic layer was washed with brine dried over magnesium sulfate concentrated to give a brown oil Purification by flash chromatography (silica gel eluting with a 10 to 30% ethyl acetate/hexane gradient)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 5-L, 3-neck, round bottom flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen bubbler was charged with 375 mL (2.84 mol) of (diethylamino)sulfur trifluoride and 400 mL of dichloromethane. The solution was cooled to −78° C. To this was added via addition funnel a solution of 304 g (1.37 mol) of benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate in 400 mL of dichloromethane over a 2-h period keeping the reaction temperature <−70° C. The reaction mixture was allowed to stir and warm slowly to ambient temperature overnight. The reaction mixture was added portion-wise with caution to a large extractor containing ice, water, and saturated aqueous sodium bicarbonate solution. The mixture was extracted with 8 L of ethyl acetate. The organic layer was washed with saturated aqueous brine, dried over magnesium sulfate, and concentrated to give a brown oil. Purification by flash chromatography (silica gel, eluting with a 10 to 30% ethyl acetate/hexane gradient) gave the title compound as a brown oil. thermocouple, addition funnel the reaction temperature <−70° C warm slowly to ambient temperature overnight The reaction mixture was added portion-wise with caution to a large extractor The mixture was extracted with 8 L of ethyl acetate The organic layer was washed with saturated aqueous brine dried over magnesium sulfate concentrated to give a brown oil Purification by flash chromatography (silica gel eluting with a 10 to 30% ethyl acetate/hexane gradient)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 5-L, 3-neck, round bottom flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen bubbler was charged with 375 mL (2.84 mol) of (diethylamino)sulfur trifluoride and 400 mL of dichloromethane. The solution was cooled to −78° C. To this was added via addition funnel a solution of 304 g (1.37 mol) of benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate in 400 mL of dichloromethane over a 2-h period keeping the reaction temperature <−70° C. The reaction mixture was allowed to stir and warm slowly to ambient temperature overnight. The reaction mixture was added portion-wise with caution to a large extractor containing ice, water, and saturated aqueous sodium bicarbonate solution. The mixture was extracted with 8 L of ethyl acetate. The organic layer was washed with saturated aqueous brine, dried over magnesium sulfate, and concentrated to give a brown oil. Purification by flash chromatography (silica gel, eluting with a 10 to 30% ethyl acetate/hexane gradient) gave the title compound as a brown oil. thermocouple, addition funnel the reaction temperature <−70° C warm slowly to ambient temperature overnight The reaction mixture was added portion-wise with caution to a large extractor The mixture was extracted with 8 L of ethyl acetate The organic layer was washed with saturated aqueous brine dried over magnesium sulfate concentrated to give a brown oil Purification by flash chromatography (silica gel eluting with a 10 to 30% ethyl acetate/hexane gradient)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 5-L, 3-neck, round bottom flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen bubbler was charged with 375 mL (2.84 mol) of (diethylamino)sulfur trifluoride and 400 mL of dichloromethane. The solution was cooled to −78° C. To this was added via addition funnel a solution of 304 g (1.37 mol) of benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate in 400 mL of dichloromethane over a 2-h period keeping the reaction temperature below −70° C. The reaction mixture was allowed to stir and warm slowly to ambient temperature overnight. The reaction mixture was added portion-wise with caution to a large extractor containing ice, water, and saturated aqueous sodium bicarbonate solution. The mixture was extracted with 8 L of ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated to give a brown oil. Purification by flash chromatography (silica gel, eluting with a 10 to 30% ethyl acetate/hexane gradient) gave the title compound as a brown oil. thermocouple, addition funnel the reaction temperature below −70° C warm slowly to ambient temperature overnight The reaction mixture was added portion-wise with caution to a large extractor The mixture was extracted with 8 L of ethyl acetate The organic layer was washed with brine dried over magnesium sulfate concentrated to give a brown oil Purification by flash chromatography (silica gel eluting with a 10 to 30% ethyl acetate/hexane gradient)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 5-L, 3-neck, round bottom flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen bubbler was charged with 375 mL (2.84 mol) of (diethylamino)sulfur trifluoride and 400 mL of dichloromethane. The solution was cooled to −78° C. To this was added via addition funnel a solution of 304 g (1.37 mol) of benzyl(3R)-3-hydroxypyrrolidine-1-carboxylate in 400 mL of dichloromethane over a 2-h period keeping the reaction temperature <−70° C. The reaction mixture was allowed to stir and warm slowly to ambient temperature overnight. The reaction mixture was added portion-wise with caution to a large extractor containing ice, water, and saturated aqueous sodium bicarbonate solution. The mixture was extracted with 8 L of ethyl acetate. The organic layer was washed with saturated aqueous brine, dried over magnesium sulfate, and concentrated to give a brown oil. Purification by flash chromatography (silica gel, eluting with a 10 to 30% ethyl acetate/hexane gradient) gave the title compound as a brown oil. thermocouple, addition funnel the reaction temperature <−70° C warm slowly to ambient temperature overnight The reaction mixture was added portion-wise with caution to a large extractor The mixture was extracted with 8 L of ethyl acetate The organic layer was washed with saturated aqueous brine dried over magnesium sulfate concentrated to give a brown oil Purification by flash chromatography (silica gel eluting with a 10 to 30% ethyl acetate/hexane gradient)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 5-L, 3-neck, round bottom flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen bubbler was charged with 375 mL (2.84 mol) of (diethylamino)sulfur trifluoride and 400 mL of dichloromethane. The solution was cooled to −78° C. To this was added via addition funnel a solution of 304 g (1.37 mol) of benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate in 400 mL of dichloromethane over a 2-h period keeping the reaction temperature below −70° C. The reaction mixture was allowed to stir and warm slowly to ambient temperature overnight. The reaction mixture was added portion-wise with caution to a large extractor containing ice, water, and saturated aqueous sodium bicarbonate solution. The mixture was extracted with 8 L of ethyl acetate. The organic layer was washed with saturated aqueous brine, dried over magnesium sulfate, and concentrated to give a brown oil. Purification by flash chromatography (silica gel, eluting with a 10 to 30% ethyl acetate/hexane gradient) gave the title compound as a brown oil. thermocouple, addition funnel the reaction temperature below −70° C warm slowly to ambient temperature overnight The reaction mixture was added portion-wise with caution to a large extractor The mixture was extracted with 8 L of ethyl acetate The organic layer was washed with saturated aqueous brine dried over magnesium sulfate concentrated to give a brown oil Purification by flash chromatography (silica gel eluting with a 10 to 30% ethyl acetate/hexane gradient)

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

実験手順: A stirred mixture of 20.85 g (0.360 moles) of potassium fluoride spray-dried and 18.0 g (0.048 moles) of (3R)-N- benzyloxycarbonyl-3-hydroxypyrrolidine in 160 ml of freshly distilled ethylene glycol was kept at 85° C. for 15 h under nitrogen atmosphere. spray-dried

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 5-L, 3-neck, round bottom flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen bubbler was charged with 375 mL (2.84 mol) of (diethylamino)sulfur trifluoride and 400 mL of dichloromethane. The solution was cooled to −78° C. To this was added via addition funnel a solution of 304 g (1.37 mol) of benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate in 400 mL of dichloromethane over a 2-h period keeping the reaction temperature below −70° C. The reaction mixture was allowed to stir and warm slowly to ambient temperature overnight. The reaction mixture was added portion-wise with caution to a large extractor containing ice, water, and saturated aqueous sodium bicarbonate solution. The mixture was extracted with 8 L of ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated to give a brown oil. Purification by flash chromatography (silica gel, eluting with a 10 to 30% ethyl acetate/hexane gradient) gave the title compound as a brown oil. thermocouple, addition funnel the reaction temperature below −70° C warm slowly to ambient temperature overnight The reaction mixture was added portion-wise with caution to a large extractor The mixture was extracted with 8 L of ethyl acetate The organic layer was washed with brine dried over magnesium sulfate concentrated to give a brown oil Purification by flash chromatography (silica gel eluting with a 10 to 30% ethyl acetate/hexane gradient)