Trifluoroacetic acid → Benzyl [(cis-4-aminocyclohexyl)methyl]carbamate

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.

1. washThe solution was washed successively with 1 N HCl, sat. NaHCO3 and brine
2. dry with materialbefore drying over Na2SO4
3. customResidual chloroformate was removed by chromatography
4. customto afford the di-protected intermediate which
5. customAfter 1 h the volatiles were removed in vacuo
6. customthe residue partitioned between sat. NaHCO3 and EtOAc

ORDレコード

ord-06698874cb80486483b8267e249c7ad2

出典データセット

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07601714B2