1-Chloro-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene → 1-Cyclohexyl-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene

HRID 1828702Notes

Reaction equation

HRID 1828702 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)=[CH:4][C:3]=1[C:19]([F:22])([F:21])[F:20]>CN1C(=O)CCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:2]1([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][O:9][CH2:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[CH:4][C:3]=2[C:19]([F:22])([F:21])[F:20])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1

Participants

4

Reactant 1

HCID 220577531-Chloro-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene

Product 1

HCID 220577361-Cyclohexyl-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 1-chloro-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene (1.5 g, 4.5 mmol) and cyclohexylzinc bromide THF solution (0.5 M, 27 mL) in NMP (30 mL) is added bis(tri-t-butylphosphine)palladium(0) (115 mg, 0.225 mmol). The mixture is purged with N2 for 5 min, followed by heating at 120° C. 12 h under N2. After cooling to room temperature, the reaction is quenched by the addition of H2O (100 mL) and aqueous HCl (1N, 20 mL). The mixture is extracted with EtOAc (3×40 mL). The combined organic phases are washed with saturated aqueous NaHCO3, saturated aqueous NaCl, and dried over Na2SO4. After concentration, the residue is purified by silica gel chromatography (5% EtOAc in hexanes) to give 1-cyclohexyl-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene as a colorless oil.

Workup

  1. customThe mixture is purged with N2 for 5 min
  2. custom12 h
  3. temperatureAfter cooling to room temperature
  4. customthe reaction is quenched by the addition of H2O (100 mL) and aqueous HCl (1N, 20 mL)
  5. extractionThe mixture is extracted with EtOAc (3×40 mL)
  6. washThe combined organic phases are washed with saturated aqueous NaHCO3, saturated aqueous NaCl
  7. dry with materialdried over Na2SO4
  8. concentrationAfter concentration
  9. customthe residue is purified by silica gel chromatography (5% EtOAc in hexanes)

Sources & evidence

ORD record
ord-085e122cf6734cf3a6b765484238f086
Source dataset
uspto-grants-2006_06
Patent number
US07060697B2

Reaction notes

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