Water → 3-(Cyclohexylmethoxy)-5-methylphenol

HRID 875580Notes

Reaction equation

HRID 875580 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([OH:8])[CH:7]=1.O.CC(C)([O-])C.[K+].Br[CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>CN(C=O)C>[CH:19]1([CH2:18][O:8][C:6]2[CH:5]=[C:4]([OH:9])[CH:3]=[C:2]([CH3:1])[CH:7]=2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

6

Reactant 4

HCID 962WaterHCID 10436OrcinolHCID 137636Cyclohexane, (bromomethyl)-HCID 23665647Potassium tert-butoxide

Product 1

HCID 230943513-(Cyclohexylmethoxy)-5-methylphenol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-methylbenzene-1,3-diol.H2O (1.0 g, 7.0 mmol) in DMF (15 ml) was added potassium tert-butoxide (0.86 g, 77 mmol). The mixture was stirred at 60° C. for 1 h. To the mixture was added (bromomethyl)cyclohexane (1.2 g, 7.0 mmol). The reaction mixture was stirred at 60° C. for 18 h, concentrated under vacuum, partitioned between water (40 ml) and ethyl acetate (60 ml). Ethyl acetate portion was dried over Na2SO4. Purification by chromatography (10 to 30% EtOAc-hexanes gradient) gave 3-(cyclohexylmethoxy)-5-methylphenol (133) as a light yellow solid. Yield (0.40 g, 26%): 1H NMR (400 MHz, CDCl3) δ 6.31 (s, 1H), 6.20-6.22 (m, 2H), 4.62 (bs, 1H), 3.69 (d, J=6.4 Hz, 2H), 2.50 (s, 3H), 1.64-1.88 (m, 6H), 1.16-1.34 (m, 3H), 0.98-1.08 (m, 2H).

Workup

  1. stirringThe reaction mixture was stirred at 60° C. for 18 h
  2. concentrationconcentrated under vacuum
  3. custompartitioned between water (40 ml) and ethyl acetate (60 ml)
  4. dry with materialEthyl acetate portion was dried over Na2SO4
  5. customPurification by chromatography (10 to 30% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-ab55c7b5ee8940478cddfba9035b403f
Source dataset
uspto-grants-2015_03
Patent number
US08981153B2

Reaction notes

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