3,3-dichloro-4,5-dihydro-1H-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:

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 (1.0 g, 4.32 mmol) and ethyl bromoacetate (0.51 ml) in of tetrahydrofuran (30 ml) was added dropwise with stirring during 15 minutes to a solution of sodium hydride (4.76 mmol) in tetrahydrofuran (20 ml) at room temperature under a nitrogen atmosphere. Stirring was continued for an additional 2 hours. The solution was quenched by addition of saturated aqueous ammonium chloride and the solvents were removed under reduced pressure. The residue was extracted with ether (3×20 ml), and the combined ether solutions washed with saturated brine (20 ml) and dried over magnesium sulfate. Removal of the solvent under reduced pressure gave 3,3-dichloro-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one. NMR(CDCl3):δ1.27 (t, 3H); 3.22 (m, 4H); 4.25 (q, 2H); 4.65 (s, 2H), 7.3 (m, 4H). The solution was quenched by addition of saturated aqueous ammonium chloride the solvents were removed under reduced pressure The residue was extracted with ether (3×20 ml) the combined ether solutions washed with saturated brine (20 ml) dried over magnesium sulfate Removal of the solvent 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 3,3-dichloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (1.0 g, 4.32 mmol) and ethyl bromoacetate (0.51 ml) in of tetrahydrofuran (30 ml) was added dropwise with stirring during 15 minutes to a solution of sodium hydride (4.76 mmol) in tetrahydrofuran (20 ml) at room temperature under a nitrogen atmosphere. Stirring was continued for an additional 2 hours. The solution was quenched by addition of saturated aqueous ammonium chloride and the solvents were removed under reduced pressure. The residue was extracted with ether (3×20 ml), and the combined ether solutions washed with saturated brine (20 ml) and dried over magnesium sulfate. Removal of the solvent under reduced pressure gave 3,3-dichloro-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one. NMR(CDCl3):δ1.27 (t, 3H); 3.22 (m, 4H); 4.25 (q, 2H); 4.65 (s, 2H), 7.3 (m, 4H). The solution was quenched by addition of saturated aqueous ammonium chloride the solvents were removed under reduced pressure The residue was extracted with ether (3×20 ml) the combined ether solutions washed with saturated brine (20 ml) dried over magnesium sulfate Removal of the solvent 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 3,3-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 mixture of 2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (48.3 g, see Briggs et al., J. Chem. Soc. 1937, 456), phosphorus pentachloride (188 g), and xylene (1300 ml) was heated with stirring under an atmosphere of nitrogen to 90° (oil bath temperature) during 30 min with pauses at 30° (to allow the phosphorus pentachloride to dissolve) and at 50°. There was a copious evolution of hydrogen chloride. The temperature was maintained at 90° for 30 minutes. The reaction mixture was filtered while hot to remove a small amount of suspended solid, and the filtrate was evaporated under reduced pressure until all the solvent was removed. The residue was added with stirring to saturated aqueous sodium carbonate (100 ml). The product was filtered after the solidification process was complete, then slurried in ethanol (150 ml), filtered, washed with ethanol (50 ml) and ether (50 ml) and dried to give 3,3-dichloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, m.p. 185°-187°. was heated to dissolve) and at 50° The temperature was maintained at 90° for 30 minutes The reaction mixture was filtered while hot to remove a small amount of suspended solid the filtrate was evaporated under reduced pressure until all the solvent was removed The residue was added with stirring to saturated aqueous sodium carbonate (100 ml) The product was filtered after the solidification process filtered washed with ethanol (50 ml) and ether (50 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 (1.0 g, 4.32 mmol) and ethyl bromoacetate (0.51 ml) in of tetrahydrofuran (30 ml) was added dropwise with stirring during 15 minutes to a solution of sodium hydride (4.76 mmol) in tetrahydrofuran (20 ml) at room temperature under a nitrogen atmosphere. Stirring was continued for an additional 2 hours. The solution was quenched by addition of saturated aqueous ammonium chloride and the solvents were removed under reduced pressure. The residue was extracted with ether (3×20 ml), and the combined ether solutions washed with saturated brine (20 ml) and dried over magnesium sulfate. Removal of the solvent under reduced pressure gave 3,3-dichloro-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one. NMR(CDCl3): δ1.27 (t, 3H); 3.22 (m, 4H); 4.25 (q, 2H); 4.65 (s, 2H), 7.3 (m, 4H). The solution was quenched by addition of saturated aqueous ammonium chloride the solvents were removed under reduced pressure The residue was extracted with ether (3×20 ml) the combined ether solutions washed with saturated brine (20 ml) dried over magnesium sulfate Removal of the solvent 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 3,3-dichloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (1.0 g, 4.32 mmol) and ethyl bromoacetate (0.51 ml) in of tetrahydrofuran (30 ml) was added dropwise with stirring during 15 minutes to a solution of sodium hydride (4.76 mmol) in tetrahydrofuran (20 ml) at room temperature under a nitrogen atmosphere. Stirring was continued for an additional 2 hours. The solution was quenched by addition of saturated aqueous ammonium chloride and the solvents were removed under reduced pressure. The residue was extracted with ether (3×20 ml), and the combined ether solutions washed with saturated brine (20 ml) and dried over magnesium sulfate. Removal of the solvent under reduced pressure gave 3,3-dichloro-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one. NMR(CDCl3): δ1.27 (t, 3H); 3.22 (m, 4H); 4.25 (q, 2H); 4.65 (s, 2H), 7.3 (m, 4H). The solution was quenched by addition of saturated aqueous ammonium chloride the solvents were removed under reduced pressure The residue was extracted with ether (3×20 ml) the combined ether solutions washed with saturated brine (20 ml) dried over magnesium sulfate Removal of the solvent 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 3,3-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 mixture of 2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (48.3 g, see Briggs et al., J. Chem. Soc. 1937, 456), phosphorus pentachloride (188 g), and xylene (1300 ml) was heated with stirring under an atmosphere of nitrogen to 90° (oil bath temperature) during 30 min with pauses at 30° (to allow the phosphorus pentachloride to dissolve) and at 50°. There was a copious evolution of hydrogen chloride. The temperature was maintained at 90° for 30 minutes. The reaction mixture was filtered while hot to remove a small amount of suspended solid, and the filtrate was evaporated under reduced pressure until all the solvent was removed. The residue was added with stirring to saturated aqueous sodium carbonate (100 ml). The product was filtered after the solidification process was complete, then slurried in ethanol (150 ml), filtered, washed with ethanol (50 ml) and ether (50 ml) and dried to give 3,3-dichloro-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, m.p. 185°-187°. was heated to dissolve) and at 50° The temperature was maintained at 90° for 30 minutes The reaction mixture was filtered while hot to remove a small amount of suspended solid the filtrate was evaporated under reduced pressure until all the solvent was removed The residue was added with stirring to saturated aqueous sodium carbonate (100 ml) The product was filtered after the solidification process filtered washed with ethanol (50 ml) and ether (50 ml) dried

反応条件: temp:0.00; pressure:0.00; stir: