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

HRID 1819478Notes

Reaction equation

HRID 1819478 reaction equation
C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH2:15])[CH2:10][CH2:9]1)(C)(C)C.C(N(CC)C(C)C)(C)C.[CH2:26]([O:33][C:34](Cl)=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:26]([O:33][C:34](=[O:35])[NH:15][CH2:14][CH:11]1[CH2:10][CH2:9][CH:8]([NH2:7])[CH2:13][CH2:12]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 2756045tert-butyl N-[4-(aminomethyl)cyclohexyl]carbamate

Product 1

HCID 59845659Benzyl [(cis-4-aminocyclohexyl)methyl]carbamateYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-06698874cb80486483b8267e249c7ad2
Source dataset
uspto-grants-2009_10
Patent number
US07601714B2

Reaction notes

Loading…