3-Chloro-1,3,4,5-tetrahydro-2H-1-benzazepin-2-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: A solution of 3-chloro-2,3,4,5-tetrahydro-1H-[1]benzazepine-2-one (1.95 g) in dimethylformamide (10 ml) was added dropwise with stirring to a solution of potassium t-butoxide (1.12 g) in dimethylformamide (10 ml) at 5°. The solution was stirred for an additional 15 minutes at 5°, then ethyl bromoacetate (1.78 g) in dimethylformamide (5 ml) was added dropwise. Stirring was continued for an additional 30 minutes at 5° and then for 3 hours at room temperature. The reaction mixture was cooled to 10° and water (100 ml) was added. The solution was extracted with chloroform (100 ml) and the chloroform solution washed with water (2×10 ml) and dried over sodium sulfate. The solvent was removed under reduced pressure to yield 3-chloro-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one; NMR(DMSO-d6):δ1.2(t,3H); 2.65(m,4H); 4.15(q,2H); 2.6(d, 2H); 7.3(m). Stirring was continued for an additional 30 minutes at 5° for 3 hours at room temperature The reaction mixture was cooled to 10° The solution was extracted with chloroform (100 ml) the chloroform solution washed with water (2×10 ml) dried over sodium sulfate The solvent was removed under reduced pressure

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

実験手順: A solution of 3-chloro-2,3,4,5-tetrahydro-1H-[1]benzazepine-2-one (1.95 g) in dimethylformamide (10 ml) was added dropwise with stirring to a solution of potassium t-butoxide (1.12 g) in dimethylformamide (10 ml) at 5°. The solution was stirred for an additional 15 minutes at 5°, then ethyl bromoacetate (1.78 g) in dimethylformamide (5 ml) was added dropwise. Stirring was continued for an additional 30 minutes at 5° and then for 3 hours at room temperature. The reaction mixture was cooled to 10° and water (100 ml) was added. The solution was extracted with chloroform (100 ml) and the chloroform solution washed with water (2×10 ml) and dried over sodium sulfate. The solvent was removed under reduced pressure to yield 3-chloro-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one; NMR(DMSO-d6):δ1.2(t,3H); 2.65(m,4H); 4.15(q,2H); 2.6(d, 2H); 7.3(m). Stirring was continued for an additional 30 minutes at 5° for 3 hours at room temperature The reaction mixture was cooled to 10° The solution was extracted with chloroform (100 ml) the chloroform solution washed with water (2×10 ml) dried over sodium sulfate The solvent was removed under reduced pressure

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

実験手順: A solution of 3-chloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (15.9 g, 0.08 mol) and sodium azide (6.36 g, 0.10 mol) in dimethylsulfoxide (320 ml) was maintained at 80° C. under an atmosphere of nitrogen for 3 hours. At this time, the IR spectrum of an aliquot showed a strong peak at 2150 cm-1 characteristic of the azide group. The reaction mixture was poured into 1000 ml of ice/water and the suspension was stirred for 30 min. The solid was filtered off, washed with water (250 ml) and dried to give 3-azido-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, m.p. 142°-145°. The solid was filtered off washed with water (250 ml) dried

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

実験手順: A solution of 3,3-dichloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (20 g, 0.174 mol) and anhydrous sodium acetate (15.4 g, 0.188 mol) in glacial acetic acid (920 ml) was hydrogenated at atmospheric pressure using 5% Pd-C (1.72 g) as catalyst until the uptake of hydrogen ceased. The catalyst was filtered off and the acetic acid evaporated under reduced pressure. The residue was equilibrated between 10% (NaHCO3 (900 ml) and dichloromethane (300 ml). The aqueous layer (pH 8) was further extracted with dichloromethane (3×300 ml) and the combined organic solutions were dried over anhydrous sodium sulfate and evaporated to give 3-chloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, m.p. 163°-167°. The catalyst was filtered off the acetic acid evaporated under reduced pressure The aqueous layer (pH 8) was further extracted with dichloromethane (3×300 ml) the combined organic solutions were dried over anhydrous sodium sulfate evaporated

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

実験手順: A solution of 3,3-dichloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (20 g, 0.174 mol) and anhydrous sodium acetate (15.4 g, 0.188 mol) in glacial acetic acid (920 ml) was hydrogenated at atmospheric pressure using 5% Pd-C (1.72 g) as catalyst until the uptake of hydrogen ceased. The catalyst was filtered off and the acetic acid evaporated under reduced pressure. The residue was equilibrated between 10% (NaHCO3 (900 ml) and dichloromethane (300 ml). The aqueous layer (pH 8) was further extracted with dichloromethane (3×300 ml) and the combined organic solutions were dried over anhydrous sodium sulfate and evaporated to give 3-chloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, m.p. 163°-167°. The catalyst was filtered off the acetic acid evaporated under reduced pressure The aqueous layer (pH 8) was further extracted with dichloromethane (3×300 ml) the combined organic solutions were dried over anhydrous sodium sulfate evaporated

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

実験手順: A solution of 3-chloro-2,3,4,5-tetrahydro-1H-[1]benzazepine-2-one (1.95 g) in dimethylformamide (10 ml) was added dropwise with stirring to a solution of potassium t-butoxide (1.12 g) in dimethylformamide (10 ml) at 5°. The solution was stirred for an additional 15 minutes at 5°, then ethyl bromoacetate (1.78 g) in dimethylformamide (5 ml) was added dropwise. Stirring was continued for an additional 30 minutes at 5° and then for 3 hours at room temperature. The reaction mixture was cooled to 10° and water (100 ml) was added. The solution was extracted with chloroform (100 ml) and the chloroform solution washed with water (2×10 ml) and dried over sodium sulfate. The solvent was removed under reduced pressure to yield 3-chloro-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one; NMR(DMSO-d6): δ1.2(t,3H); 2.65(m,4H); 4.15(q,2H); 2.6 (d,2H); 7.3(m). Stirring was continued for an additional 30 minutes at 5° for 3 hours at room temperature The reaction mixture was cooled to 10° The solution was extracted with chloroform (100 ml) the chloroform solution washed with water (2×10 ml) dried over sodium sulfate The solvent was removed under reduced pressure

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

実験手順: A solution of 3-chloro-2,3,4,5-tetrahydro-1H-[1]benzazepine-2-one (1.95 g) in dimethylformamide (10 ml) was added dropwise with stirring to a solution of potassium t-butoxide (1.12 g) in dimethylformamide (10 ml) at 5°. The solution was stirred for an additional 15 minutes at 5°, then ethyl bromoacetate (1.78 g) in dimethylformamide (5 ml) was added dropwise. Stirring was continued for an additional 30 minutes at 5° and then for 3 hours at room temperature. The reaction mixture was cooled to 10° and water (100 ml) was added. The solution was extracted with chloroform (100 ml) and the chloroform solution washed with water (2×10 ml) and dried over sodium sulfate. The solvent was removed under reduced pressure to yield 3-chloro-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one; NMR(DMSO-d6): δ1.2(t,3H); 2.65(m,4H); 4.15(q,2H); 2.6 (d,2H); 7.3(m). Stirring was continued for an additional 30 minutes at 5° for 3 hours at room temperature The reaction mixture was cooled to 10° The solution was extracted with chloroform (100 ml) the chloroform solution washed with water (2×10 ml) dried over sodium sulfate The solvent was removed under reduced pressure

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

実験手順: A solution of 3-chloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (15.9 g, 0.08 mol) and sodium azide (6.36 g, 0.10 mol) in dimethylsulfoxide (320 ml) was maintained at 80° C. under an atmosphere of nitrogen for 3 hours. At this time, the IR spectrum of an aliquot showed a strong peak at 2150 cm-1 characteristic of the azide group. The reaction mixture was poured into 1000 ml of ice/water and the suspension was stirred for 30 min. The solid was filtered off, washed with water (250 ml) and dried to give 3-azido-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, m.p. 142°-5°. The solid was filtered off washed with water (250 ml) dried

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

実験手順: A solution of 3,3-dichloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (20 g, 0.174 mol) and anhydrous sodium acetate (15.4 g, 0.188 mol) in glacial acetic acid (920 ml) was hydrogenated at atmospheric pressure using 5% Pd-C (1.72 g) as catalyst until the uptake of hydrogen ceased. The catalyst was filtered off and the acetic acid evaporated under reduced pressure. The residue was equilibrated between 10% NaHCO3 (900 ml) and dichloromethane (300 ml). The aqueous layer (pH 8) was further extracted with dichloromethane (3×300 ml) and the combined organic solutions were dried over anhydrous sodium sulfate and evaporated to give 3-chloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, m.p. 163°-167°. The catalyst was filtered off the acetic acid evaporated under reduced pressure The aqueous layer (pH 8) was further extracted with dichloromethane (3×300 ml) the combined organic solutions were dried over anhydrous sodium sulfate evaporated

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: A solution of 3-chloro-2,3,4,5-tetrahydro-1H-[1]benzazepine-2-one (1.95 g) in dimethylformamide (10 ml) was added dropwise with stirring to a solution of potassium t-butoxide (1.12 g) in dimethylformamide (10 ml) at 5°. The solution was stirred for an additional 15 minutes at 5°, then ethyl bromoacetate (1.78 g) in dimethylformamide (5 ml) was added dropwise. Stirring was continued for an additional 30 minutes at 5° and then for 3 hours at room temperature. The reaction mixture was cooled to 10° and water (100 ml) was added. The solution was extracted with chloroform (100 ml) and the chloroform solution washed with water (2×10 ml) and dried over sodium sulfate. The solvent was removed under reduced pressure to yield 3-chloro-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one; NMR(DMSO-d6): δ1.2(t,3H); 2.65(m,4H); 4.15(q,2H); 2.6(d,2H); 7.3(m). Stirring was continued for an additional 30 minutes at 5° for 3 hours at room temperature The reaction mixture was cooled to 10° The solution was extracted with chloroform (100 ml) the chloroform solution washed with water (2×10 ml) dried over sodium sulfate The solvent was removed under reduced pressure