1-(4-amino-3,5-difluorophenyl)ethanone

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

実験手順: To a solution of 1-(4-amino-3,5-difluoro-phenyl)-ethanone (2.35 g, 13.73 mmol) and Et3N (2 mL) in CH2Cl2 (10 mL) was added dropwise MsCl (2.34 mL, 2.34 mmol) at 0° C. The mixture was stirred for 3 hours at room temperature. The mixture was then diluted with EtOAc and 1N-HCl. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was used directly in the following reaction. The crude residue was dissolved in THF (8 mL), after then was added 1N NaOH (4 mL) and CH3OH (4 mL) to the solution. After stirred for 5 hrs at room temperature, the mixture was diluted with EtOAc and 1N-HCl. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by chromatography to afford N-(4-acetyl-2,6-difluoro-phenyl)-methanesulfonamide (1.85 g, 54%). The organic layer was washed with water and brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The crude product was used directly in the following reaction After stirred for 5 hrs at room temperature The organic layer was washed with water and brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The crude residue was purified by chromatography

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

実験手順: To a solution of 1-(4-amino-3,5-difluoro-phenyl)-ethanone (2.35 g, 13.73 mmol) and Et3N (2 mL) in CH2Cl2 (10 mL) was added dropwise MsCl (2.34 mL, 2.34 mmol) at 0° C. The mixture was stirred for 3 hours at room temperature. The mixture was then diluted with EtOAc and 1N-HCl. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was used directly in the following reaction. The crude residue was dissolved in THF (8 mL), after then was added 1N NaOH (4 mL) and CH3OH (4 mL) to the solution. After stirred for 5 hrs at room temperature, the mixture was diluted with EtOAc and 1N-HCl. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by chromatography to afford N-(4-acetyl-2,6-difluoro-phenyl)-methanesulfonamide (1.85 g, 54%). The organic layer was washed with water and brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The crude product was used directly in the following reaction After stirred for 5 hrs at room temperature The organic layer was washed with water and brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The crude residue was purified by chromatography

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

実験手順: To a solution of 1-(4-amino-3,5-difluoro-phenyl)-ethanone (2.35 g, 13.73 mmol) and Et3N (2 mL) in CH2Cl2 (10 mL) was added dropwise MsCl (2.34 mL, 2.34 mmol) at 0° C. The mixture was stirred for 3 hours at room temperature. The mixture was then diluted with EtOAc and 1N-HCl. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was used directly in the following reaction. The crude residue was dissolved in THF (8 mL), after then was added 1N NaOH (4 mL) and CH3OH (4 mL) to the solution. After stirred for 5 hrs at room temperature, the mixture was diluted with EtOAc and 1N-HCl. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by chromatography to afford N-(4-acetyl-2,6-difluoro-phenyl)-methanesulfonamide (1.85 g, 54%). The organic layer was washed with water and brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The crude product was used directly in the following reaction After stirred for 5 hrs at room temperature The organic layer was washed with water and brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The crude residue was purified by chromatography

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

実験手順: A suspension of 2,6-difluoro-4-iodoaniline (1 g, 3.92 mmol) and Pd(OAc)2 (0.025 eq), DPPP (0.05 eq) in [bmim][3F3] (6 mL) was stirred for 10 min. After the mixture was degassed three times, butyl vinyl ether (5 eq) and Et3N (1.2 eq) were injected sequentially. The mixture was stirred for 15 hrs at 115° C. The mixture cooled to room temperature, and then was added 1N-HCl. After the mixture was stirred for 0.5 hour, CH2Cl2 was added. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by chromatography to give 1-(4-amino-3,5-difluoro-phenyl)-ethanone (300 mg, 45%). The mixture was stirred for 15 hrs at 115° C After the mixture was stirred for 0.5 hour The organic layer was washed with brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The crude residue was purified by chromatography

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

実験手順: A suspension of 2,6-difluoro-4-iodoaniline (1 g, 3.92 mmol) and Pd(OAc)2 (0.025 eq), DPPP (0.05 eq) in [bmim][3F3] (6 mL) was stirred for 10 min. After the mixture was degassed three times, butyl vinyl ether (5 eq) and Et3N (1.2 eq) were injected sequentially. The mixture was stirred for 15 hrs at 115° C. The mixture cooled to room temperature, and then was added 1N-HCl. After the mixture was stirred for 0.5 hour, CH2Cl2 was added. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by chromatography to give 1-(4-amino-3,5-difluoro-phenyl)-ethanone (300 mg, 45%). The mixture was stirred for 15 hrs at 115° C After the mixture was stirred for 0.5 hour The organic layer was washed with brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The crude residue was purified by chromatography

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

実験手順: A suspension of 2,6-difluoro-4-iodoaniline (1 g, 3.92 mmol) and Pd(OAc)2 (0.025 eq), DPPP (0.05 eq) in [bmim][3F3] (6 mL) was stirred for 10 min. After the mixture was degassed three times, butyl vinyl ether (5 eq) and Et3N (1.2 eq) were injected sequentially. The mixture was stirred for 15 hrs at 115° C. The mixture cooled to room temperature, and then was added 1N-HCl. After the mixture was stirred for 0.5 hour, CH2Cl2 was added. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by chromatography to give 1-(4-amino-3,5-difluoro-phenyl)-ethanone (300 mg, 45%). The mixture was stirred for 15 hrs at 115° C After the mixture was stirred for 0.5 hour The organic layer was washed with brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The crude residue was purified by chromatography