benzyl N-[(4-aminocyclohexyl)methyl]carbamate

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: To a solution of (4-amino-cyclohexylmethyl)-carbamic acid benzyl ester (350 mg, 1.34 mmol) in DMF (5 mL) was added K2CO3 (924 mg, 6.70 mmol) and 1,4-dibromobutane (160 mL, 1.34 mmol). The reaction mixture was stirred at room temperature for 14 h before diluting with EtOAc (100 mL). The reaction solution was washed with water (2×100 mL) and brine before concentrating in vacuo. The residue was purified by chromatography using a 12 g ISCO combi-flash cartridge (silica gel, 95:4.75:0.25 DCM/MeOH/NH4OH) to afford (4-pyrrolidin-1-yl-cyclohexylmethyl)-carbamic acid benzyl ester (351 mg, 83%) as an off-white solid. The reaction solution was washed with water (2×100 mL) and brine before concentrating in vacuo The residue was purified by chromatography

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

実験手順: To a stirred slurry of (4-aminomethyl-cyclohexyl)-carbamic acid tert-butyl ester (500 mg, 2.19 mmol) and N,N-diisopropylethylamine (382 μL, 2.63 mmol) in DCM (8 mL) at 0° C. under N2 was added benzylchloroformate (311 μL, 2.41 mmol) dropwise via syringe. After 30 min the reaction was allowed to warm to room temperature and stirred for a further 2 h before diluting with DCM (50 mL). The solution was washed successively with 1 N HCl, sat. NaHCO3 and brine before drying over Na2SO4. Residual chloroformate was removed by chromatography using a 12 g ISCO combi-flash cartridge (silica gel, 90:10 to 50:50 hexane/EtOAc) to afford the di-protected intermediate which was treated directly with DCM (2 mL) and TFA (2 mL). After 1 h the volatiles were removed in vacuo and the residue partitioned between sat. NaHCO3 and EtOAc. Concentration of the organic layer in vacuo afforded (4-amino-cyclohexylmethyl)-carbamic acid benzyl ester (517 mg, 90%) as a white solid. The solution was washed successively with 1 N HCl, sat. NaHCO3 and brine before drying over Na2SO4 Residual chloroformate was removed by chromatography to afford the di-protected intermediate which After 1 h the volatiles were removed in vacuo the residue partitioned between sat. NaHCO3 and EtOAc