1,5-dihydro-4,1-benzoxazepin-2-one

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

実験手順: 1 g o-amino-benzyloxy acetic acid and 1.1 g dicyclohexyl carbodiimide were stirred in 15 ml refluxing methanol for 8 hours. The mixture was evaporated, and the residue was stirred with 50 ml acetone and filtered, whereafter the filtrate was evaporated to give the title compound. M.p. 160°-165° C. The mixture was evaporated filtered, whereafter the filtrate was evaporated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1,5-dihydro-4,1-benzoxazepin-2-one (3.7 g, 22.7 mmol) in THF (75 mL) cooled with an ice bath was added lithium aluminum hydride (2.6 g, 68 mmole) portion wise. The reaction mixture was warmed to 80° C. and stirred for 2 hrs. This mixture was then cooled to rt and was treated with water (2.7 mL), 10% sodium hydroxide aqueous solution (2.7 mL) and water (8.1 mL). The resulting mixture was stirred for another 10 minutes before filtration through Celite. The Celite was washed with ethyl acetate and the organic solution was washed with brine (30 mL×2) before drying over MgSO4. Concentration of the filtrate and purification of the residue by silica gel column chromatography eluting with chloroform/methanol (99/1) yielded 1,2,3,5-tetrahydro-4,1-benzoxazepine 2-2 as a brown solid (1.65 g, 48% yield). MS: 150.0 (M+H)+; tR=1.02 min (method 1). This mixture was then cooled to rt The resulting mixture was stirred for another 10 minutes before filtration through Celite The Celite was washed with ethyl acetate the organic solution was washed with brine (30 mL×2) before drying over MgSO4 Concentration of the filtrate and purification of the residue by silica gel column chromatography eluting with chloroform/methanol (99/1)

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

実験手順: To 2-chloro-N-(2-hydroxymethyl-phenyl)acetamide (7.0 g, 35 mmol) in isopropyl alcohol (100 mL) was added 50% w/w sodium hydroxide aqueous solution (4 mL, 50 mmol). The mixture was stirred at rt overnight. The mixture was extracted with DCM (50 mL×2). The resulting solution was then washed with brine (50 mL×2) and dried over MgSO4. The solvent was evaporated to afford 1,5-dihydro-4,1-benzoxazepin-2-one as a brown solid in 65% yield (3.7 g). MS: 163.0 (M+H)+; tR=1.56 min (method 1). The mixture was extracted with DCM (50 mL×2) The resulting solution was then washed with brine (50 mL×2) dried over MgSO4 The solvent was evaporated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1,5-dihydro-4,1-benzoxazepin-2-one (3.7 g, 22.7 mmol) in THF (75 mL) cooled with an ice bath was added lithium aluminum hydride (2.6 g, 68 mmole) portion wise. The reaction mixture was warmed to 80° C. and stirred for 2 hrs. This mixture was then cooled to rt and was treated with water (2.7 mL), 10% sodium hydroxide aqueous solution (2.7 mL) and water (8.1 mL). The resulting mixture was stirred for another 10 minutes before filtration through Celite. The Celite was washed with ethyl acetate and the organic solution was washed with brine (30 mL×2) before drying over MgSO4. Concentration of the filtrate and purification of the residue by silica gel column chromatography eluting with chloroform/methanol (99/1) yielded 1,2,3,5-tetrahydro-4,1-benzoxazepine 2-2 as a brown solid (1.65 g, 48% yield). MS: 150.0 (M+H)+; tR=1.02 min (method 1). This mixture was then cooled to rt The resulting mixture was stirred for another 10 minutes before filtration through Celite The Celite was washed with ethyl acetate the organic solution was washed with brine (30 mL×2) before drying over MgSO4 Concentration of the filtrate and purification of the residue by silica gel column chromatography eluting with chloroform/methanol (99/1)

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

実験手順: To 2-chloro-N-(2-hydroxymethyl-phenyl)acetamide (7.0 g, 35 mmol) in isopropyl alcohol (100 mL) was added 50% w/w sodium hydroxide aqueous solution (4 mL, 50 mmol). The mixture was stirred at rt overnight. The mixture was extracted with DCM (50 mL×2). The resulting solution was then washed with brine (50 mL×2) and dried over MgSO4. The solvent was evaporated to afford 1,5-dihydro-4,1-benzoxazepin-2-one as a brown solid in 65% yield (3.7 g). MS: 163.0 (M+H)+; tR=1.56 min (method 1). The mixture was extracted with DCM (50 mL×2) The resulting solution was then washed with brine (50 mL×2) dried over MgSO4 The solvent was evaporated

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

実験手順: 1 g o-amino-benzyloxy acetic acid and 1.1 g dicyclohexyl carbodiimide were stirred in 15 ml refluxing methanol for 8 hours. The mixture was evaporated, and the residue was stirred with 50 ml acetone and filtered, whereafter the filtrate was evaporated to give the title compound. M.p. 160°-165° C. The mixture was evaporated filtered, whereafter the filtrate was evaporated

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

実験手順: 1 g o-amino-benzyloxy acetic acid and 1.1 g dicyclohexyl carbodiimide were stirred in 15 ml refluxing methanol for 8 hours. The mixture was evaporated, and the residue was stirred with 50 ml acetone and filtered, whereafter the filtrate was evaporated to give the title compound. The mixture was evaporated filtered, whereafter the filtrate was evaporated

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

実験手順: 1 g o-amino-benzyloxy acetic acid and 1.1 g dicyclohexyl carbodiimide were stirred in 15 ml refluxing methanol for 8 hours. The mixture was evaporated, and the residue was stirred with 50 ml acetone and filtered, whereafter the filtrate was evaporated to give the title compound. M.p. 160°-165° C. The mixture was evaporated filtered, whereafter the filtrate was evaporated