7-methylazepan-2-one

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (95%, 1.74 g, 68.7 mmol, 1.15 equiv) was added to a solution of 7-methylazepan-2-one (2-2, 7.60 g, 59.8 mmol, 1 equiv) in THF (150 mL) at 0° C. and the resulting mixture was warmed to 23° C. and stirred for 20 h. Benzyl bromide (7.82 mL, 65.7 mmol, 1.10 equiv) was added followed by 2 drops of water, and the resulting mixture was stirred at 23° C. for 20 h. Excess sodium hydride was quenched carefully with water and the mixture was concentrated. The residue was partitioned between water and dichloromethane. The organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (100% hexanes initially, grading to 100% EtOAc) to give 1-benzyl-7-methylazepan-2-one (2-3) as a colorless oil. LRMS m/z (M+H) 218.2 found, 218.2 required. the resulting mixture was stirred at 23° C. for 20 h Excess sodium hydride was quenched carefully with water the mixture was concentrated The residue was partitioned between water and dichloromethane The organic layer was dried over sodium sulfate concentrated The residue was purified by flash column chromatography (100% hexanes initially

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (95%, 1.74 g, 68.7 mmol, 1.15 equiv) was added to a solution of 7-methylazepan-2-one (2-2, 7.60 g, 59.8 mmol, 1 equiv) in THF (150 mL) at 0° C. and the resulting mixture was warmed to 23° C. and stirred for 20 h. Benzyl bromide (7.82 mL, 65.7 mmol, 1.10 equiv) was added followed by 2 drops of water, and the resulting mixture was stirred at 23° C. for 20 h. Excess sodium hydride was quenched carefully with water and the mixture was concentrated. The residue was partitioned between water and dichloromethane. The organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (100% hexanes initially, grading to 100% EtOAc) to give 1-benzyl-7-methylazepan-2-one (2-3) as a colorless oil. LRMS m/z (M+H) 218.2 found, 218.2 required. the resulting mixture was stirred at 23° C. for 20 h Excess sodium hydride was quenched carefully with water the mixture was concentrated The residue was partitioned between water and dichloromethane The organic layer was dried over sodium sulfate concentrated The residue was purified by flash column chromatography (100% hexanes initially

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methanesulfonic acid (15 mL) was added to a solution of 2-methylcyclohexanone (2-1, 6.00 g, 53.5 mmol, 1 equiv) in DME (20 mL) at −40° C. Sodium azide (8.69 g, 134 mmol, 2.50 equiv) was added in four equal portions over 1 h as cooling was maintained. The cold bath was then removed and the reaction mixture was warmed to 23° C. and stirred for 20 h. The mixture was diluted with DME (20 mL) and basified to pH 9 with concentrated aqueous ammonium hydroxide solution. The resulting mixture was partitioned between brine (200 mL) and ethyl actetate (4×200 mL). The combined organic layers were dried over sodium sulfate and concentrated to give 7-methylazepan-2-one (2-2) as a pasty white solid. 1H NMR (300 MHz, CDCl3) δ 5.50 (br s, 1H), 3.50 (m, 1H), 2.43 (m, 2H), 2.05-1.30 (m, 6H), 1.21 (d, 3H,J=7.1 Hz). as cooling was maintained The cold bath was then removed The mixture was diluted with DME (20 mL) The resulting mixture was partitioned between brine (200 mL) and ethyl The combined organic layers were dried over sodium sulfate concentrated

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (95%, 1.74 g, 68.7 mmol, 1.15 equiv) was added to a solution of 7-methylazepan-2-one (2-2, 7.60 g, 59.8 mmol, 1 equiv) in THF (150 mL) at 0° C. and the resulting mixture was warmed to 23° C. and stirred for 20 h. Benzyl bromide (7.82 mL, 65.7 mmol, 1.10 equiv) was added followed by 2 drops of water, and the resulting mixture was stirred at 23° C. for 20 h. Excess sodium hydride was quenched carefully with water and the mixture was concentrated. The residue was partitioned between water and dichloromethane. The organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (100% hexanes initially, grading to 100% EtOAc) to give 1-benzyl-7-methylazepan-2-one (2-3) as a colorless oil. LRMS m/z (M+H) 218.2 found, 218.2 required. the resulting mixture was stirred at 23° C. for 20 h Excess sodium hydride was quenched carefully with water the mixture was concentrated The residue was partitioned between water and dichloromethane The organic layer was dried over sodium sulfate concentrated The residue was purified by flash column chromatography (100% hexanes initially

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methanesulfonic acid (15 mL) was added to a solution of 2-methylcyclohexanone (2-1, 6.00 g, 53.5 mmol, 1 equiv) in DME (20 mL) at −40° C. Sodium azide (8.69 g, 134 mmol, 2.50 equiv) was added in four equal portions over 1 h as cooling was maintained. The cold bath was then removed and the reaction mixture was warmed to 23° C. and stirred for 20 h. The mixture was diluted with DME (20 mL) and basified to pH 9 with concentrated aqueous ammonium hydroxide solution. The resulting mixture was partitioned between brine (200 mL) and ethyl actetate (4×200 mL). The combined organic layers were dried over sodium sulfate and concentrated to give 7-methylazepan-2-one (2-2) as a pasty white solid. 1H NMR (300 MHz, CDCl3) δ 5.50 (br s, 1H), 3.50 (m, 1H), 2.43 (m, 2H), 2.05-1.30 (m, 6H), 1.21 (d, 3H,J=7.1 Hz). as cooling was maintained The cold bath was then removed The mixture was diluted with DME (20 mL) The resulting mixture was partitioned between brine (200 mL) and ethyl The combined organic layers were dried over sodium sulfate concentrated