Acetonitrile → N-[3-(Benzyloxy)propyl]-4-methylcyclohexan-1-amine

HRID 2043916Notes

Reaction equation

HRID 2043916 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][CH2:9][CH2:10][O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:19](#[N:21])[CH3:20]>>[CH2:12]([O:11][CH2:10][CH2:9][CH2:8][NH:21][CH:19]1[CH2:15][CH2:14][CH:13]([CH3:18])[CH2:12][CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

4

Reactant 3

HCID 6342Acetonitrile2×HCID 11430Potassium CarbonateHCID 2776064Benzyl 3-Bromopropyl Ether

Product 1

HCID 66961973N-[3-(Benzyloxy)propyl]-4-methylcyclohexan-1-amine

Procedure

4-Trans-methyl-cyclohexylamine (6.65 g, 44.4 mmol) and potassium carbonate (12.3 g, 88.8 mmol) in acetonitrile (50 mL) was heated to reflux before a solution of (3-bromo-propoxymethyl)-benzene (10.2 g, 44.4 mmol) in acetonitrile (25 mL) over a period of 30 min. The reaction mixture was refluxed for 2 hours before the solvent was removed in vacuo. The residue was divided between diethyl ether (100 mL) and aqueous sodium hydroxide (1N, 50 mL). The organic phase was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified using column chromatography (SiO2, heptane-ethyl acetate 1:1) to give 8.4 g (3-benzyloxy-propyl)-(4-methyl-cyclohexyl)-amine. To this was added a solution of bis-tert-butyldicarbonate (32 mmol, 1N in THF) and the reaction mixture was stirred at room temperature for 18 hours before the solvent was removed in vacuo. The residue was dissolved in diethyl ether (150 mL) and washed with water (2×100 mL). The organic phase was dried (MgSO4), filtered and concentrated in vacuo to give 10.6 g of (3-benzyloxy-propyl)-(4-methylcyclohexyl)-carbamic acid tert-butyl ester. This was subsequently dissolved ethanol (100 mL) and Pd/C (10%, 1 g) was added. The reaction mixture was stirred under H2 (1 atm) for 4 hours. The reaction mixture was filtered through a pad of celite and concentrated in vacuo to give 7.9 g of (3-hydroxy-propyl)-(4-methyl-cyclohexyl)-carbamic acid tert-butyl ester.

Workup

  1. temperatureThe reaction mixture was refluxed for 2 hours before the solvent
  2. customwas removed in vacuo
  3. dry with materialThe organic phase was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified

Sources & evidence

ORD record
ord-322aa7585f0d4245ad4e1a3c47fe02a8
Source dataset
uspto-grants-2013_11
Patent number
US08586614B2

Reaction notes

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