2-(anilinomethyl)-4-bromophenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 2 Carbonyldiimidazole (0.874 g, 5.39 mmol) and DMAP (0.088 g, 0.719 mmol) were added to a solution of 4-bromo-2-((phenylamino)methyl)phenol (1.00 g, 3.60 mmol) in DCM (100 mL) and the resulting mixture was stirred at rt for 60 h. The mixture was diluted with hexanes (100 mL), washed with NaHCO3 (aq) (2×25 mL), 1 M hydrochloric acid (25 mL) and brine (25 mL), dried and filtered through a pad of silica gel. The solids were rinsed with 1:1 EtOAc-hexane and the filtrate was concentrated to give 6-bromo-3-phenyl-3,4-dihydro-2H-benzo[e][1,3]oxazin-2-one as a white solid (1.09 g, 100%). 1H NMR (400 MHz, DMSO-d6) δ 7.41-7.56 (3H, m), 7.30-7.41 (3H, m), 7.21-7.29 (1H, m), 7.01 (1H, d, J=8.80 Hz), 4.80 (2H, s). Mass spectrum m/z 304, 306 (M+H)+. washed with NaHCO3 (aq) (2×25 mL), 1 M hydrochloric acid (25 mL) and brine (25 mL) dried filtered through a pad of silica gel The solids were rinsed with 1:1 EtOAc-hexane the filtrate was concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 1 Aniline (1.50 mL, 16.42 mmol) was added to a solution of 5-bromo-2-hydroxybenzaldehyde (3.00 g, 14.92 mmol) in 1,2-dichloroethane (100 mL). After 10 min at rt, sodium triacetoxyborohydride (4.74 g, 22.39 mmol) was added. The mixture was stirred at rt. After four days, additional aniline (1.50 mL, 16.42 mmol) and sodium triacetoxyborohydride (4.74 g, 22.39 mmol) were added. After two more days, saturated aqueous ammonium chloride (200 mL) was added. The mixture was stirred at rt for 3 h. The phases were separated and the aqueous phase was extracted with DCM (2×50 mL). The combined organic phases were dried and concentrated. The residue was treated with toluene (25 mL) and hexanes (25 mL) and the mixture was stirred for 30 min. The precipitate was washed with 1:1 mixture of toluene-hexanes (3 mL) and dried under vacuum to give 4-bromo-2-((phenylamino)methyl)phenol as a white solid (2.64 g, 64%). 1H NMR (400 MHz, DMSO-d6) δ 8.70 (1H, br. s.), 7.18-7.46 (4H, m), 6.95 (1H, t, J=7.48 Hz), 6.80-6.90 (2H, m), 6.77 (1H, d, J=8.58 Hz), 4.39 (2H, s), 3.98 (1H, br. s.). Mass spectrum m/z 278, 280 (M+H)+. After four days The mixture was stirred at rt for 3 h The phases were separated the aqueous phase was extracted with DCM (2×50 mL) The combined organic phases were dried concentrated The residue was treated with toluene (25 mL) and hexanes (25 mL) the mixture was stirred for 30 min The precipitate was washed with 1:1 mixture of toluene-hexanes (3 mL) dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 1 Aniline (1.50 mL, 16.42 mmol) was added to a solution of 5-bromo-2-hydroxybenzaldehyde (3.00 g, 14.92 mmol) in 1,2-dichloroethane (100 mL). After 10 min at rt, sodium triacetoxyborohydride (4.74 g, 22.39 mmol) was added. The mixture was stirred at rt. After four days, additional aniline (1.50 mL, 16.42 mmol) and sodium triacetoxyborohydride (4.74 g, 22.39 mmol) were added. After two more days, saturated aqueous ammonium chloride (200 mL) was added. The mixture was stirred at rt for 3 h. The phases were separated and the aqueous phase was extracted with DCM (2×50 mL). The combined organic phases were dried and concentrated. The residue was treated with toluene (25 mL) and hexanes (25 mL) and the mixture was stirred for 30 min. The precipitate was washed with 1:1 mixture of toluene-hexanes (3 mL) and dried under vacuum to give 4-bromo-2-((phenylamino)methyl)phenol as a white solid (2.64 g, 64%). 1H NMR (400 MHz, DMSO-d6) δ 8.70 (1H, br. s.), 7.18-7.46 (4H, m), 6.95 (1H, t, J=7.48 Hz), 6.80-6.90 (2H, m), 6.77 (1H, d, J=8.58 Hz), 4.39 (2H, s), 3.98 (1H, br. s.). Mass spectrum m/z 278, 280 (M+H)+. After four days The mixture was stirred at rt for 3 h The phases were separated the aqueous phase was extracted with DCM (2×50 mL) The combined organic phases were dried concentrated The residue was treated with toluene (25 mL) and hexanes (25 mL) the mixture was stirred for 30 min The precipitate was washed with 1:1 mixture of toluene-hexanes (3 mL) dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 2 Carbonyldiimidazole (0.874 g, 5.39 mmol) and DMAP (0.088 g, 0.719 mmol) were added to a solution of 4-bromo-2-((phenylamino)methyl)phenol (1.00 g, 3.60 mmol) in DCM (100 mL) and the resulting mixture was stirred at rt for 60 h. The mixture was diluted with hexanes (100 mL), washed with NaHCO3 (aq) (2×25 mL), 1 M hydrochloric acid (25 mL) and brine (25 mL), dried and filtered through a pad of silica gel. The solids were rinsed with 1:1 EtOAc-hexane and the filtrate was concentrated to give 6-bromo-3-phenyl-3,4-dihydro-2H-benzo[e][1,3]oxazin-2-one as a white solid (1.09 g, 100%). 1H NMR (400 MHz, DMSO-d6) δ 7.41-7.56 (3 H, m), 7.30-7.41 (3 H, m), 7.21-7.29 (1 H, m), 7.01 (1 H, d, J=8.80 Hz), 4.80 (2 H, s). Mass spectrum m/z 304, 306 (M+H)+. washed with NaHCO3 (aq) (2×25 mL), 1 M hydrochloric acid (25 mL) and brine (25 mL) dried filtered through a pad of silica gel The solids were rinsed with 1:1 EtOAc-hexane the filtrate was concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 1 Aniline (1.50 mL, 16.42 mmol) was added to a solution of 5-bromo-2-hydroxybenzaldehyde (3.00 g, 14.92 mmol) in 1,2-dichloroethane (100 mL). After 10 min at rt, sodium triacetoxyborohydride (4.74 g, 22.39 mmol) was added. The mixture was stirred at rt. After four days, additional aniline (1.50 mL, 16.42 mmol) and sodium triacetoxyborohydride (4.74 g, 22.39 mmol) were added. After two more days, saturated aqueous ammonium chloride (200 mL) was added. The mixture was stirred at rt for 3 h. The phases were separated and the aqueous phase was extracted with DCM (2×50 mL). The combined organic phases were dried and concentrated. The residue was treated with toluene (25 mL) and hexanes (25 mL) and the mixture was stirred for 30 min. The precipitate was washed with 1:1 mixture of toluene-hexanes (3 mL) and dried under vacuum to give 4-bromo-2-((phenylamino)methyl)phenol as a white solid (2.64 g, 64%). 1H NMR (400 MHz, DMSO-d6) δ 8.70 (1 H, br. s.), 7.18-7.46 (4 H, m), 6.95 (1 H, t, J=7.48 Hz), 6.80-6.90 (2 H, m), 6.77 (1 H, d, J=8.58 Hz), 4.39 (2 H, s), 3.98 (1 H, br. s.). Mass spectrum m/z 278, 280 (M+H)+. After four days The mixture was stirred at rt for 3 h The phases were separated the aqueous phase was extracted with DCM (2×50 mL) The combined organic phases were dried concentrated The residue was treated with toluene (25 mL) and hexanes (25 mL) the mixture was stirred for 30 min The precipitate was washed with 1:1 mixture of toluene-hexanes (3 mL) dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 2 Carbonyldiimidazole (0.874 g, 5.39 mmol) and DMAP (0.088 g, 0.719 mmol) were added to a solution of 4-bromo-2-((phenylamino)methyl)phenol (1.00 g, 3.60 mmol) in DCM (100 mL) and the resulting mixture was stirred at rt for 60 h. The mixture was diluted with hexanes (100 mL), washed with NaHCO3 (aq) (2×25 mL), 1 M hydrochloric acid (25 mL) and brine (25 mL), dried and filtered through a pad of silica gel. The solids were rinsed with 1:1 EtOAc-hexane and the filtrate was concentrated to give 6-bromo-3-phenyl-3,4-dihydro-2H-benzo[e][1,3]oxazin-2-one as a white solid (1.09 g, 100%). 1H NMR (400 MHz, DMSO-d6) δ 7.41-7.56 (3H, m), 7.30-7.41 (3H, m), 7.21-7.29 (1H, m), 7.01 (1H, d, J=8.80 Hz), 4.80 (2H, s). Mass spectrum m/z 304, 306 (M+H)+. washed with NaHCO3 (aq) (2×25 mL), 1 M hydrochloric acid (25 mL) and brine (25 mL) dried filtered through a pad of silica gel The solids were rinsed with 1:1 EtOAc-hexane the filtrate was concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step 1 Aniline (1.50 mL, 16.42 mmol) was added to a solution of 5-bromo-2-hydroxybenzaldehyde (3.00 g, 14.92 mmol) in 1,2-dichloroethane (100 mL). After 10 min at rt, sodium triacetoxyborohydride (4.74 g, 22.39 mmol) was added. The mixture was stirred at rt. After four days, additional aniline (1.50 mL, 16.42 mmol) and sodium triacetoxyborohydride (4.74 g, 22.39 mmol) were added. After two more days, saturated aqueous ammonium chloride (200 mL) was added. The mixture was stirred at rt for 3 h. The phases were separated and the aqueous phase was extracted with DCM (2×50 mL). The combined organic phases were dried and concentrated. The residue was treated with toluene (25 mL) and hexanes (25 mL) and the mixture was stirred for 30 min. The precipitate was washed with 1:1 mixture of toluene-hexanes (3 mL) and dried under vacuum to give 4-bromo-2-((phenylamino)methyl)phenol as a white solid (2.64 g, 64%). 1H NMR (400 MHz, DMSO-d6) δ 8.70 (1H, br. s.), 7.18-7.46 (4H, m), 6.95 (1H, t, J=7.48 Hz), 6.80-6.90 (2H, m), 6.77 (1H, d, J=8.58 Hz), 4.39 (2H, s), 3.98 (1H, br. s.). Mass spectrum m/z 278, 280 (M+H)+. After four days The mixture was stirred at rt for 3 h The phases were separated the aqueous phase was extracted with DCM (2×50 mL) The combined organic phases were dried concentrated The residue was treated with toluene (25 mL) and hexanes (25 mL) the mixture was stirred for 30 min The precipitate was washed with 1:1 mixture of toluene-hexanes (3 mL) dried under vacuum