7-fluoro-1,3,4,5-tetrahydro-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:

反応条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 7-fluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (411 mg, 2.3 mmol) (Step A) dissolved in a mixture of 7.9 mL of dry methylene chloride and 1.0 mL of dry tetrahydrofuran was treated with 1.62 mL (1.18 g, 11.6 mmol, 5 eq) of triethylamine and the resulting solution cooled to -15° C. Iodotrimethylsilane (0.66 mL, 932 mg, 4.7 mmol, 2 eq) was added followed by 1.183 g of iodine (4.7 mmol, 2 eq) added in small portions over 5 minutes. The mixture was warmed to room temperature over 5 minutes at which time 15 mL of methylene chloride was added followed by 20 mL of 10% aqueous sodium sulfite. The layers were separated and the organic layer washed with 10% sodium sulfite (3×20 mL). The aqueous layer was further extracted with 20 mL of methylene chloride. The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated to dryness under vacuum. The crude product was chromatographed on silica gel, eluting with methylene chloride/methanol (99:1) to afford 511 mg (1.68 mmol, 73%) of the product. 1H NMR (300MHz, CDCl3): 2.70 (m,3H), 2.93 (m,1H), 4.62 (t,9Hz,1H), 6.95 (m,3H), 7.86 (br s,1H). FAB-MS: calculated for C10H9FINO 305; found 306 (M+H,100%). added in small portions over 5 minutes was added The layers were separated the organic layer washed with 10% sodium sulfite (3×20 mL) The aqueous layer was further extracted with 20 mL of methylene chloride The combined extracts were washed with brine dried over magnesium sulfate filtered concentrated to dryness under vacuum The crude product was chromatographed on silica gel eluting with methylene chloride/methanol (99:1)

反応条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 7-fluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (411 mg, 2.3 mmol) (Step A) dissolved in a mixture of 7.9 mL of dry methylene chloride and 1.0 mL of dry tetrahydrofuran was treated with 1.62 mL (1.18 g, 11.6 mmol, 5 eq) of triethylamine and the resulting solution cooled to -15° C. Iodotrimethylsilane (0.66 mL, 932 mg, 4.7 mmol, 2 eq) was added followed by 1.183 g of iodine (4.7 mmol, 2 eq) added in small portions over 5 minutes. The mixture was warmed to room temperature over 5 minutes at which time 15 mL of methylene chloride was added followed by 20 mL of 10% aqueous sodium sulfite. The layers were separated and the organic layer washed with 10% sodium sulfite (3×20 mL). The aqueous layer was further extracted with 20 mL of methylene chloride. The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated to dryness under vacuum. The crude product was chromatographed on silica gel, eluting with methylene chloride/methanol (99:1) to afford 511 mg (1.68 mmol, 73%) of the product. 1H NMR (300MHz, CDCl3): 2.70 (m,3H), 2.93 (m,1H), 4.62 (t,9Hz,1H), 6.95 (m,3H), 7.86 (br s,1H). FAB-MS: calculated for C10H9FINO 305; found 306 (M+H,100%). added in small portions over 5 minutes was added The layers were separated the organic layer washed with 10% sodium sulfite (3×20 mL) The aqueous layer was further extracted with 20 mL of methylene chloride The combined extracts were washed with brine dried over magnesium sulfate filtered concentrated to dryness under vacuum The crude product was chromatographed on silica gel eluting with methylene chloride/methanol (99:1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium azide 1.1 g (16.92 mmol) was added to a mixture of 6.0 mL of chloroform and 1.1 mL of water at 0° C. Concentrated sulfuric acid (0.44 mL) was added dropwise and the mixture stirred at 0° C. for two hours then filtered. The chloroform layer containing hydrazoic acid was added to a solution of 1.3 g (7.92 mmol) of 6-fluoro-1-tetralone (prepared by the method of Allinger and Jones, J. Org. Chem., 27, 70-76 (1962)) in 4.8 mL of chloroform. Additional sulfuric acid (2.16 mL) was added dropwise with stirring while maintaining the temperature below 40° C. The mixture was stirred at 40° C. for two hours then at room temperature for 16 hours. The mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was added to ice; the resulting recipitate was extracted with methylene chloride (5x). The combined extracts were washed with brine, dried over magnesium sulfate and filtered through a silica plug. Solvents were removed under vacuum to afford 162 mg (0.92 mmol, 11%) of the product. 1H NMR (300MHz, CDCl3): 2.21 (m,2H), 2.32 (t,7Hz,2H), 2.7 (t,7Hz,2H), 6.93 (m,3H), 7.8 (br s,1H). FAB-MS: calculated for C10H10FNO 179; found 180 (M+H,100%). then filtered The chloroform layer containing hydrazoic acid prepared by the method of Allinger and Jones, J with stirring while maintaining the temperature below 40° C The mixture was stirred at 40° C. for two hours at room temperature for 16 hours The mixture was transferred to a separatory funnel the layers were separated The aqueous layer was added to ice the resulting recipitate was extracted with methylene chloride (5x) The combined extracts were washed with brine dried over magnesium sulfate filtered through a silica plug Solvents were removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 7-fluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (411 mg, 2.3 mmol) (Step A) dissolved in a mixture of 7.9 mL of dry methylene chloride and 1.0 mL of dry tetrahydrofuran was treated with 1.62 mL (1.18 g, 11.6 mmol, 5 eq) of triethylamine and the resulting solution cooled to -15° C. Iodotrimethylsilane (0.66 mL, 932 mg, 4.7 mmol, 2 eq) was added followed by 1.183 g of iodine (4.7 mmol, 2 eq) added in small portions over 5 minutes. The mixture was warmed to room temperature over 5 minutes at which time 15 mL of methylene chloride was added followed by 20 mL of 10% aqueous sodium sulfite. The layers were separated and the organic layer washed with 10% sodium sulfite (3×20 mL). The aqueous layer was further extracted with 20 mL of methylene chloride. The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated to dryness under vacuum. The crude product was chromatographed on silica gel, eluting with methylene chloride/methanol (99:1) to afford 511 mg (1.68 mmol, 73%) of the product. 1H NMR (300 MHz, CDCl3): 2.70 (m,3H), 2.93 (m,1H), 4.62 (t,9 Hz,1H), 6.95 (m,3H), 7.86 (br s,1H). FAB-MS: calculated for C10H9FINO 305; found 306 (M+H,100%). added in small portions over 5 minutes was added The layers were separated the organic layer washed with 10% sodium sulfite (3×20 mL) The aqueous layer was further extracted with 20 mL of methylene chloride The combined extracts were washed with brine dried over magnesium sulfate filtered concentrated to dryness under vacuum The crude product was chromatographed on silica gel eluting with methylene chloride/methanol (99:1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium azide 1.1 g (16.92 mmol) was added to a mixture of 6.0 mL of chloroform and 1.1 mL of water at 0° C. Concentrated sulfuric acid (0.44 mL) was added dropwise and the mixture stirred at 0° C. for two hours then filtered. The chloroform layer containing hydrazoic acid was added to a solution of 1.3 g (7.92 mmol) of 6-fluoro-1-tetralone (prepared by the method of Allinger and Jones, J. Org. Chem., 27, 70-76 (1962)) in 4.8 mL of chloroform. Additional sulfuric acid (2.16 mL) was added dropwise with stirring while maintaining the temperature below 40° C. The mixture was stirred at 40° C. for two hours then at room temperature for 16 hours. The mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was added to ice; the resulting precipitate was extracted with methylene chloride (5×). The combined extracts were washed with brine, dried over magnesium sulfate and filtered through a silica plug. Solvents were removed under vacuum to afford 162 mg (0.92 mmol,11%) of the product. 1H NMR (300 MHz, CDCl3): 2.21 (m,2H), 2.32 (t,7 Hz,2H), 2.77 (t,7 Hz,2H), 6.93 (m,3H), 7.8 (br s,1H). FAB-MS: calculated for C10H10FNO 179; found 180 (M+H,100%). then filtered The chloroform layer containing hydrazoic acid prepared by the method of Allinger and Jones, J with stirring while maintaining the temperature below 40° C The mixture was stirred at 40° C. for two hours at room temperature for 16 hours The mixture was transferred to a separatory funnel the layers were separated The aqueous layer was added to ice the resulting precipitate was extracted with methylene chloride (5×) The combined extracts were washed with brine dried over magnesium sulfate filtered through a silica plug Solvents were removed under vacuum

反応条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 7-fluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (411 mg, 2.3 mmol) (Step A) dissolved in a mixture of 7.9 mL of dry methylene chloride and 1.0 mL of dry tetrahydrofuran was treated with 1.62 mL (1.18 g, 11.6 mmol, 5 eq) of triethylamine and the resulting solution cooled to -15° C. Iodotrimethylsilane (0.66 mL, 932 mg, 4.7 mmol, 2 eq) was added followed by 1.183 g of iodine (4.7 mmol, 2 eq) added in small portions over 5 minutes. The mixture was warmed to room temperature over 5 minutes at which time 15 mL of methylene chloride was added followed by 20 mL of 10% aqueous sodium sulfite. The layers were separated and the organic layer washed with 10% sodium sulfite (3×20 mL). The aqueous layer was further extracted with 20 mL of methylene chloride. The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated to dryness under vacuum. The crude product was chromatographed on silica gel, eluting with methylene chloride/methanol (99:1) to afford 511 mg (1.68 mmol, 73%) of the product. 1H NMR (300MHz, CDCl3): 2.70 (m,3H), 2.93 (m,1H), 4.62 (t,9Hz,1H), 6.95 (m,3H), 7.86 (br s,1H). FAB-MS: calculated for C10H9FINO 305; found 306 (M+H,100%). added in small portions over 5 minutes was added The layers were separated the organic layer washed with 10% sodium sulfite (3×20 mL) The aqueous layer was further extracted with 20 mL of methylene chloride The combined extracts were washed with brine dried over magnesium sulfate filtered concentrated to dryness under vacuum The crude product was chromatographed on silica gel eluting with methylene chloride/methanol (99:1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium azide 1.1 g (16.92 mmol) was added to a mixture of 6.0 mL of chloroform and 1.1 mL of water at 0° C. Concentrated sulfuric acid (0.44 mL) was added dropwise and the mixture stirred at 0° C. for two hours then filtered. The chloroform layer containing hydrazoic acid was added to a solution of 1.3 g (7.92 mmol) of 6-fluoro-1-tetralone (prepared by the method of Allinger and Jones, J. Org. Chem., 27, 70-76 (1962)) in 4.8 mL of chloroform. Additional sulfuric acid (2.16 mL) was added dropwise with stirring while maintaining the temperature below 40° C. The mixture was stirred at 40° C. for two hours then at room temperature for 16 hours. The mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was added to ice; the resulting recipitate was extracted with methylene chloride (5x). The combined extracts were washed with brine, dried over magnesium sulfate and filtered through a silica plug. Solvents were removed under vacuum to afford 162 mg (0.92 mmol, 11%) of the product. 1H NMR (300MHz, CDCl3): 2.21 (m,2H), 2.32 (t,7Hz,2H), 2.7 (t,7Hz,2H), 6.93 (m,3H), 7.8 (br s,1H). FAB-MS: calculated for C10H10FNO 179; found 180 (M+H,100%). then filtered The chloroform layer containing hydrazoic acid prepared by the method of Allinger and Jones, J with stirring while maintaining the temperature below 40° C The mixture was stirred at 40° C. for two hours at room temperature for 16 hours The mixture was transferred to a separatory funnel the layers were separated The aqueous layer was added to ice the resulting recipitate was extracted with methylene chloride (5x) The combined extracts were washed with brine dried over magnesium sulfate filtered through a silica plug Solvents were removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir: