methyl N-(2,4-difluorophenyl)carbamate

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

実験手順: Into a reaction flask under nitrogen, diisopropylamine (24.87 g, 250 mmol) is combined with 160 mL of anhydrous tetrahydrofuran and the solution is cooled to −78° C. n-Butyllithium (154 mL, 1.6 M in hexanes, 250 mmol) is added dropwise, maintaining the temperature below −70° C. After stirring at −78° C. for 1 hour, (2,4-difluoro-phenyl)-carbamic acid methyl ester (2, 20.00 g, 110 mmol) in 40 mL of tetrahydrofuran is added dropwise, maintaining the temperature below −70° C. The reaction is stirred at −78° C. for 1 hour, then warmed to room temperature and stirred for 1 minute. The reaction is poured into 250 mL of water, the pH is adjusted to 1 with addition of 2M hydrochloric acid, and the mixture is extracted with 3×250 mL of ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is slurried in hexane and the resulting solid is collected by filtration and dried to provide the desired compound (3, 19.38 g, 84%). is added dropwise maintaining the temperature below −70° C maintaining the temperature below −70° C The reaction is stirred at −78° C. for 1 hour warmed to room temperature stirred for 1 minute the mixture is extracted with 3×250 mL of ethyl acetate dried over magnesium sulfate filtered the filtrate concentrated under vacuum the resulting solid is collected by filtration dried

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a reaction flask under nitrogen, 2,4-difluoro-phenylamine (1, 50.00 g, 390 mmol) is combined with 550 mL of anhydrous dichloromethane and anhydrous pyridine (61.27 g, 770 mmol). Methyl chloroformate (43.92 g, 460 mmol) is added dropwise while cooling to maintain the temperature in the range of 20-30° C. The reaction is stirred overnight, then concentrated under vacuum. The resulting material is diluted with 250 mL of water, adjusted to pH 2 with 2M hydrochloric acid, and extracted with 3×250 mL of ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is slurried from hexane and the resulting solid is collected by filtration and dried to provide the desired compound (2, 71.06 g, 98%). while cooling concentrated under vacuum The resulting material is diluted with 250 mL of water extracted with 3×250 mL of ethyl acetate dried over magnesium sulfate filtered the filtrate concentrated under vacuum the resulting solid is collected by filtration dried

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

実験手順: Into a reaction flask under nitrogen, diisopropylamine (24.87 g, 250 mmol) is combined with 160 mL of anhydrous tetrahydrofuran and the solution is cooled to −78° C. n-Butyllithium (154 mL, 1.6 M in hexanes, 250 mmol) is added dropwise, maintaining the temperature below −70° C. After stirring at −78° C. for 1 hour, (2,4-difluoro-phenyl)-carbamic acid methyl ester (2, 20.00 g, 110 mmol) in 40 mL of tetrahydrofuran is added dropwise, maintaining the temperature below −70° C. The reaction is stirred at −78° C. for 1 hour, then warmed to room temperature and stirred for 1 minute. The reaction is poured into 250 mL of water, the pH is adjusted to 1 with addition of 2M hydrochloric acid, and the mixture is extracted with 3×250 mL of ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is slurried in hexane and the resulting solid is collected by filtration and dried to provide the desired compound (3, 19.38 g, 84%). is added dropwise maintaining the temperature below −70° C maintaining the temperature below −70° C The reaction is stirred at −78° C. for 1 hour warmed to room temperature stirred for 1 minute the mixture is extracted with 3×250 mL of ethyl acetate dried over magnesium sulfate filtered the filtrate concentrated under vacuum the resulting solid is collected by filtration dried

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a reaction flask under nitrogen, 2,4-difluoro-phenylamine (1, 50.00 g, 390 mmol) is combined with 550 mL of anhydrous dichloromethane and anhydrous pyridine (61.27 g, 770 mmol). Methyl chloroformate (43.92 g, 460 mmol) is added dropwise while cooling to maintain the temperature in the range of 20-30° C. The reaction is stirred overnight, then concentrated under vacuum. The resulting material is diluted with 250 mL of water, adjusted to pH 2 with 2M hydrochloric acid, and extracted with 3×250 mL of ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is slurried from hexane and the resulting solid is collected by filtration and dried to provide the desired compound (2, 71.06 g, 98%). while cooling concentrated under vacuum The resulting material is diluted with 250 mL of water extracted with 3×250 mL of ethyl acetate dried over magnesium sulfate filtered the filtrate concentrated under vacuum the resulting solid is collected by filtration dried

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

実験手順: Into a reaction flask under nitrogen, diisopropylamine (24.87 g, 250 mmol) is combined with 160 mL of anhydrous tetrahydrofuran and the solution is cooled to −78° C. n-Butyllithium (154 mL, 1.6 M in hexanes, 250 mmol) is added dropwise, maintaining the temperature below −70° C. After stirring at −78° C. for 1 hour, (2,4-difluoro-phenyl)-carbamic acid methyl ester (2, 20.00 g, 110 mmol) in 40 mL of tetrahydrofuran is added dropwise, maintaining the temperature below −70° C. The reaction is stirred at −78° C. for 1 hour, then warmed to room temperature and stirred for 1 minute. The reaction is poured into 250 mL of water, the pH is adjusted to 1 with addition of 2M hydrochloric acid, and the mixture is extracted with 3×250 mL of ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is slurried in hexane and the resulting solid is collected by filtration and dried to provide the desired compound (3, 19.38 g, 84%). is added dropwise maintaining the temperature below −70° C maintaining the temperature below −70° C The reaction is stirred at −78° C. for 1 hour warmed to room temperature stirred for 1 minute the mixture is extracted with 3×250 mL of ethyl acetate dried over magnesium sulfate filtered the filtrate concentrated under vacuum the resulting solid is collected by filtration dried

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a reaction flask under nitrogen, 2,4-difluoro-phenylamine (1, 50.00 g, 390 mmol) is combined with 550 mL of anhydrous dichloromethane and anhydrous pyridine (61.27 g, 770 mmol). Methyl chloroformate (43.92 g, 460 mmol) is added dropwise while cooling to maintain the temperature in the range of 20-30° C. The reaction is stirred overnight, then concentrated under vacuum. The resulting material is diluted with 250 mL of water, adjusted to pH 2 with 2M hydrochloric acid, and extracted with 3×250 mL of ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is slurried from hexane and the resulting solid is collected by filtration and dried to provide the desired compound (2, 71.06 g, 98%). while cooling concentrated under vacuum The resulting material is diluted with 250 mL of water extracted with 3×250 mL of ethyl acetate dried over magnesium sulfate filtered the filtrate concentrated under vacuum the resulting solid is collected by filtration dried