8-benzyl-8-azabicyclo[3.2.1]octan-2-one

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

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

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 8-benzyl-2-hydroxy-8-azabicyclo[3.2.1]oct-2-ene-3-carboxylate (68 mg, 0.249 mmol) in pyridine (2.5 ml) was added NaI (746 mg, 4.98 mmol). The reaction mixture was then reflux at 120° C. for 7.5 hr. The reaction mixture was concentrated and placed under vacuum. The residue was then partitioned between EtOAc and water. The aqueous phase was separated and extracted with EtOAc. All organic phases were combined, washed with saturated aqueous Na2S2O3 solution, dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-40% EtOAc/Hex to give the product 8-benzyl-8-azabicyclo[3.2.1]octan-2-one (39.4 mg, 0.183 mmol) as a syrup. Anal. Calcd. for C14H17NO m/z 215.1, found: 216.1 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.35-7.21 (5 H, m), 3.68 (2 H, s), 3.36 (2 H, d, J=5.5 Hz), 2.45-2.28 (2 H, m), 2.27-2.16 (3 H, m), 1.81-1.70 (3 H, m). The reaction mixture was concentrated The residue was then partitioned between EtOAc and water The aqueous phase was separated extracted with EtOAc washed with saturated aqueous Na2S2O3 solution dried over MgSO4 filtered concentrated The resulting residue was purified eluting with a gradient of 0-40% EtOAc/Hex

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 8-benzyl-2-hydroxy-8-azabicyclo[3.2.1]oct-2-ene-3-carboxylate (68 mg, 0.249 mmol) in pyridine (2.5 ml) was added NaI (746 mg, 4.98 mmol). The reaction mixture was then reflux at 120° C. for 7.5 hr. The reaction mixture was concentrated and placed under vacuum. The residue was then partitioned between EtOAc and water. The aqueous phase was separated and extracted with EtOAc. All organic phases were combined, washed with saturated aqueous Na2S2O3 solution, dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-40% EtOAc/Hex to give the product 8-benzyl-8-azabicyclo[3.2.1]octan-2-one (39.4 mg, 0.183 mmol) as a syrup. Anal. Calcd. for C14H17NO m/z 215.1, found: 216.1 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.35-7.21 (5 H, m), 3.68 (2 H, s), 3.36 (2 H, d, J=5.5 Hz), 2.45-2.28 (2 H, m), 2.27-2.16 (3 H, m), 1.81-1.70 (3 H, m). The reaction mixture was concentrated The residue was then partitioned between EtOAc and water The aqueous phase was separated extracted with EtOAc washed with saturated aqueous Na2S2O3 solution dried over MgSO4 filtered concentrated The resulting residue was purified eluting with a gradient of 0-40% EtOAc/Hex

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 8-benzyl-2-hydroxy-8-azabicyclo[3.2.1]oct-2-ene-3-carboxylate (68 mg, 0.249 mmol) in pyridine (2.5 ml) was added NaI (746 mg, 4.98 mmol). The reaction mixture was then reflux at 120° C. for 7.5 hr. The reaction mixture was concentrated and placed under vacuum. The residue was then partitioned between EtOAc and water. The aqueous phase was separated and extracted with EtOAc. All organic phases were combined, washed with saturated aqueous Na2S2O3 solution, dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-40% EtOAc/Hex to give the product 8-benzyl-8-azabicyclo[3.2.1]octan-2-one (39.4 mg, 0.183 mmol) as a syrup. Anal. Calcd. for C14H17NO m/z 215.1, found: 216.1 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.35-7.21 (5 H, m), 3.68 (2 H, s), 3.36 (2 H, d, J=5.5 Hz), 2.45-2.28 (2 H, m), 2.27-2.16 (3 H, m), 1.81-1.70 (3 H, m). The reaction mixture was concentrated The residue was then partitioned between EtOAc and water The aqueous phase was separated extracted with EtOAc washed with saturated aqueous Na2S2O3 solution dried over MgSO4 filtered concentrated The resulting residue was purified eluting with a gradient of 0-40% EtOAc/Hex

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

Procedure: A 5N sodium hydroxide solution (1.62 mL, 0.5 equiv.) was added to (±)-8-benzyl-8-aza-bicyclo[3.2.1]octan-2-one (3.49 g, 16.2 mmol), followed by a solution of benzaldehyde (2.59 mL, 2.69 g, 16.2 mmol) in ethanol (160 mL). The solution was stirred at ambient temperature for 4.5 h. The solution was concentrated under reduced pressure, and the residue was taken up in dichloromethane (160 mL). The mixture was washed with water (160 mL) and brine (160 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure to give crude product (4.96 g, theoretical yield 4.92 g) as an orange oil. The solution was concentrated under reduced pressure The mixture was washed with water (160 mL) and brine (160 mL) dried (sodium sulfate) filtered the solvent evaporated under reduced pressure