Benzyl Bromide → trans-4-(Dibenzylamino)cyclohexanol

HRID 2280714Notes

Reaction equation

HRID 2280714 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([OH:9])[CH2:5][CH2:4]1.[CH2:10](Br)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:8]1[CH:3]([N:2]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:4][CH2:5][CH:6]([OH:9])[CH2:7]1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 178479278HCID 178479278, compound

Product 1

HCID 22484911trans-4-(Dibenzylamino)cyclohexanolYield 39.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

trans-4-Aminocyclohexanol hydrochloride (25 g, 217 mmol) was suspended in acetonitrile (500 mL). Benzyl bromide (54.2 mL, 456 mmol) and potassium carbonate (120 g, 868 mmol) were added to the suspension and the resulting mixture was stirred vigorously overnight at room temperature. The reaction mixture was filtered through a plug of celite and the plug was washed thoroughly with acetonitrile. The filtrate was condensed to give a white solid. The crude solids were purified by silica gel chromatography (0-60% ethyl acetate in hexanes). Pure product containing fractions were combined and concentrated to afford (1r,4r)-4-(dibenzylamino)cyclohexanol (25 g, 85 mmol, 39.0% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.26-7.36 (m, 8H), 7.16-7.22 (m, 2H), 4.43 (d, J=4.69 Hz, 1H), 3.55 (s, 4H), 3.27-3.33 (m, 1H), 2.28-2.40 (m, 1H), 1.69-1.88 (m, 4H), 1.40 (qd, J=12.56, 2.93 Hz, 2H), 0.89-1.05 (m, 2H); MS (ESI) m/z 296.3 [M+1]+.

Workup

  1. filtrationThe reaction mixture was filtered through a plug of celite
  2. washthe plug was washed thoroughly with acetonitrile
  3. customcondensed
  4. customto give a white solid
  5. customThe crude solids were purified by silica gel chromatography (0-60% ethyl acetate in hexanes)
  6. additionPure product containing fractions
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-fb1a5a8a8b4e4fd88039c3c1f8eb6550
Source dataset
uspto-grants-2015_09
Patent number
US09139534B2

Reaction notes

Loading…