Ethanol → Carbamic acid, [(1R,2S)-2-(methylamino)cyclohexyl]-, 1,1-dimethylethyl ester, rel-

HRID 1526255Notes

Reaction equation

HRID 1526255 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12].[CH2:16](O)C.N1(CO)C2C=CC=CC=2N=N1.[BH4-].[Na+]>C(OCC)(=O)C>[CH3:16][NH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13]

Participants

6

Reactant 4

HCID 702EthanolHCID 2241691H-Benzotriazole-1-methanolHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 4311764Sodium borohydride

Product 1

HCID 58822134Carbamic acid, [(1R,2S)-2-(methylamino)cyclohexyl]-, 1,1-dimethylethyl ester, rel-

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of tert-butyl [(1S,2R)-2-aminocyclohexyl]carbamate (500 mg) and ethanol (10 mL) was added 1H-benzotriazol-1-yl methanol (350 mg), followed by stirring at room temperature for 7 hours. Sodium borohydride (180 mg) was added thereto under ice-cooling, followed by stirring at room temperature for 15 hours. To the reactant were added ethyl acetate and a saturated aqueous sodium hydrogen carbonate solution, followed by liquid separation. The organic phase was dried over anhydrous magnesium sulfate and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-190:9:1) to obtain tert-butyl [(1S,2R)-2-(methylamino)cyclohexyl]carbamate (174 mg) as a pale yellow oily material.

Workup

  1. temperatureunder ice-cooling
  2. stirringby stirring at room temperature for 15 hours
  3. customa saturated aqueous sodium hydrogen carbonate solution, followed by liquid separation
  4. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-190:9:1)

Sources & evidence

ORD record
ord-5bbf4a26e81a441382d4159180947d66
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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