7-bromo-2-methyl-4H-1,4-benzoxazin-3-one

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

実験手順: In 56 ml of glacial acetic acid, 6 g of 2-methyl-1,4-benzoxazin-3-(4H)-one is precooled at 0° C. and mixed drop by drop with 1.9 ml of bromine in 19 ml of glacial acetic acid. It is allowed to reach room temperature and stirred for another 8 hours. The mixture is poured onto ice water, the crystals are suctioned off and washed with water. 9.3 g of crude product results, which is recrystallized from ethanol/water. 7-Bromo-2-methyl-1,4-benzoxazin-3-(4H)-one is obtained as a by-product. As an alternative, 4-bromo-2-aminophenol can also be reacted according to the described processes. is precooled at 0° C. to reach room temperature The mixture is poured onto ice water washed with water 9.3 g of crude product results which is recrystallized from ethanol/water

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

実験手順: Borane dimethyl sulfide complex (2 M solution in THF, 0.414 mL, 0.828 mmol) was added at room temperature to a solution of 7-bromo-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one A-2 (100.0 mg, 0.414 mmol) in anhydrous THF (4.10 mL) under an atmosphere of argon. The reaction mixture was heated to reflux for 2 h, cooled to room temperature, quenched with methanol (1.0 mL), stirred for 30 mins and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient) to give 7-bromo-2-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine A-3 (92.9 mg, Yield=98%). MS (ESI) [M+1]+ 228, 230. The reaction mixture was heated to reflux for 2 h quenched with methanol (1.0 mL) concentrated to dryness under reduced pressure The crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient)

反応条件: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,8-Diazabicyclo[5.4.0]undec-7-ene (145.0 μL, 0.975 mmol) was added at room temperature to a solution of 2-amino-5-bromophenol A-1 (200.0 mg, 1.064 mmol) and methyl 2-bromoacetate (115.0 μL, 0.886 mmol) in anhydrous 1-methylpyrrolidin-2-one (4.20 mL) under an atmosphere of argon, in a 10 mL microwave reactor vial. The sealed reaction mixture was heated at 180° C. for 3 mins under microwave irradiation and then diluted with ethyl acetate (25 mL). The organic layer was washed with brine (3×20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient) to give 7-bromo-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one A-2 (217.0 mg, Yield=100%). MS (ESI) [M+1]+ 242, 244. The sealed reaction mixture The organic layer was washed with brine (3×20 mL) dried over anhydrous magnesium sulfate filtered concentrated to dryness under reduced pressure The crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient)

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

実験手順: In 56 ml of glacial acetic acid, 6 g of 2-methyl-1,4-benzoxazin-3-(4H)-one is precooled at 0° C. and mixed drop by drop with 1.9 ml of bromine in 19 ml of glacial acetic acid. It is allowed to reach room temperature and stirred for another 8 hours. The mixture is poured onto ice water, the crystals are suctioned off and washed with water. 9.3 g of crude product results, which is recrystallized from ethanol/water. 7-Bromo-2-methyl-1,4-benzoxazin-3-(4H)-one is obtained as a by-product. As an alternative, 4-bromo-2-aminophenol can also be reacted according to the described processes. is precooled at 0° C. to reach room temperature The mixture is poured onto ice water washed with water 9.3 g of crude product results which is recrystallized from ethanol/water

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

実験手順: Borane dimethyl sulfide complex (2 M solution in THF, 0.414 mL, 0.828 mmol) was added at room temperature to a solution of 7-bromo-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one A-2 (100.0 mg, 0.414 mmol) in anhydrous THF (4.10 mL) under an atmosphere of argon. The reaction mixture was heated to reflux for 2 h, cooled to room temperature, quenched with methanol (1.0 mL), stirred for 30 mins and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient) to give 7-bromo-2-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine A-3 (92.9 mg, Yield=98%). MS (ESI) [M+1]+ 228, 230. The reaction mixture was heated to reflux for 2 h quenched with methanol (1.0 mL) concentrated to dryness under reduced pressure The crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient)

反応条件: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,8-Diazabicyclo[5.4.0]undec-7-ene (145.0 μL, 0.975 mmol) was added at room temperature to a solution of 2-amino-5-bromophenol A-1 (200.0 mg, 1.064 mmol) and methyl 2-bromoacetate (115.0 μL, 0.886 mmol) in anhydrous 1-methylpyrrolidin-2-one (4.20 mL) under an atmosphere of argon, in a 10 mL microwave reactor vial. The sealed reaction mixture was heated at 180° C. for 3 mins under microwave irradiation and then diluted with ethyl acetate (25 mL). The organic layer was washed with brine (3×20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient) to give 7-bromo-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one A-2 (217.0 mg, Yield=100%). MS (ESI) [M+1]+ 242, 244. The sealed reaction mixture The organic layer was washed with brine (3×20 mL) dried over anhydrous magnesium sulfate filtered concentrated to dryness under reduced pressure The crude residue was purified by flash column chromatography on silica gel (hexanes:ethyl acetate gradient)