8-bromo-2,2-dimethyl-4H-1,4-benzoxazin-3-one

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: Using the above procedure, but starting with 8-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine (prepared by reducing 8-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one, which in turn was prepared from 2-amino-6-bromophenol and 2-bromo-2-methylproprionyl bromide via the procedure described by Van Hes et al., WO 01/14330) and 2-fluorobenzenesulfonyl chloride, 8-bromo-4-(2-fluorobenzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine was obtained as a white solid. MP.: 108.0-110.1°. prepared

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

実験手順: Using the above procedure, but starting with 8-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine (prepared by reducing 8-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one, which in turn was prepared from 2-amino-6-bromophenol and 2-bromo-2-methylproprionyl bromide via the procedure described by Van Hes et al., WO 01/14330) and 2-fluorobenzenesulfonyl chloride, 8-bromo-4-(2-fluorobenzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine was obtained as a white solid. MP.: 108.0-110.1°. prepared

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The 2-bromo-N-(3-bromo-2-hydroxy-phenyl)-2-methyl-propionamide of step 1 was dissolved in DMF (200 ml), and the DMF solution was added to K2CO3 (6.3 g, 45.58 mmol). The mixture was heated overnight at 150° C., then cooled and poured into a mixture of water/ethyl acetate. The organic fraction was washed with brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by flash chromatography to give 8-Bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one as a white solid (84.6%). MS: (M−H)−256. cooled The organic fraction was washed with brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue 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: Using the above procedure, but starting with 8-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine (prepared by reducing 8-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one, which in turn was prepared from 2-amino-6-bromophenol and 2-bromo-2-methylproprionyl bromide via the procedure described by Van Hes et al., WO 01/14330) and 2-fluorobenzenesulfonyl chloride, 8-bromo-4-(2-fluorobenzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine was obtained as a white solid. MP.: 108.0-110.1°. prepared

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: 8-Bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one from step 2 (768.30 mg, 3.0 mmol) was dissolved in dry tetrahydrofuran (THF) and the solution was heated to reflux. 0.3 ml of 10M borane dimethyl sulfide (BH3.DMS) in THF was added drop-wise to the reaction mix, and the reaction mix was kept heated under reflux for 1 hour. A solution of 10% ethanolic HCl was then added drop-wise to the reaction mix until a white precipitate appeared, after which refluxing was continued for 10 minutes. The reaction mix was cooled, and the precipitate was removed by filtration, washed with ether, and air dried to yield 770 mg of 8-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine hydrochloride (92%) as a white solid. MS: (M+H) 280. the solution was heated to reflux mix the reaction mix was kept heated under reflux for 1 hour mix until a white precipitate after which refluxing The reaction mix was cooled the precipitate was removed by filtration washed with ether, and air dried

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The 2-bromo-N-(3-bromo-2-hydroxy-phenyl)-2-methyl-propionamide of step 1 was dissolved in DMF (200 ml), and to the DMF solution was added to K2CO3 (6.3 g, 45.58 mmol). The mixture was heated overnight at 150° C., then cooled and poured into a mixture of water/ethyl acetate. The organic fraction was washed with brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by flash chromatography to give 8-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one as a white solid (84.6%). MS: (M−H)− 256. cooled The organic fraction was washed with brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue 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: Using the above procedure, but starting with 8-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine (prepared by reducing 8-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one, which in turn was prepared from 2-amino-6-bromophenol and 2-bromo-2-methylproprionyl bromide via the procedure described by Van Hes et al., WO 01/14330) and 2-fluorobenzenesulfonyl chloride, 8-bromo-4-(2-fluorobenzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine was obtained as a white solid. MP.: 108.0-110.1°. prepared

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The 2-bromo-N-(3-bromo-2-hydroxy-phenyl)-2-methyl-propionamide of step 1 was dissolved in DMF (200 ml), and the DMF solution was added to K2CO3 (6.3 g, 45.58 mmol). The mixture was heated overnight at 150° C., then cooled and poured into a mixture of water/ethyl acetate. The organic fraction was washed with brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by flash chromatography to give 8-Bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one as a white solid (84.6%). MS: (M−H)−256. cooled The organic fraction was washed with brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue 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: Using the above procedure, but starting with 8-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine (prepared by reducing 8-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one, which in turn was prepared from 2-amino-6-bromophenol and 2-bromo-2-methylproprionyl bromide via the procedure described by Van Hes et al., WO 01/14330) and 2-fluorobenzenesulfonyl chloride, 8-bromo-4-(2-fluorobenzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine was obtained as a white solid. MP.: 108.0-110.1°. prepared