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

Participants

Reaction Conditions

Reaction Steps

1-Chloro-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene (2 g, 6.51 mmol), Pd(t-Bu3P)2 (66.54 mg, 0.13 mmol) and cyclohexylzinc bromide/THF solution (0.5 M, 40 mL, 19.5 mmol) are mixed in 1-methyl-2-pyrrolidinone (NMP) (40 mL). The mixture is purged with N2 (g) and then heated at 105° C. for 16 hours. The reaction mixture is poured into saturated aqueous NH4Cl (250 mL) and extracted with EtOAc. The combined extracts are washed with brine and dried over Na2SO4. After concentration, the residue is purified by silica gel chromatography (8:1 hexanes/EtOAc) to give 1-Cyclohexyl-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene. To a solution of this material in DCM (8 mL) is added TFA (8 mL). The reaction mixture is stirred at room temperature for 16 hours. After concentration, the residue is partitioned between saturated aqueous NH4Cl and EtOAc. The aqueous phase is extracted with EtOAc. The combined organic extracts are washed with brine and dried over Na2SO4. After concentration, the residue is purified by silica gel chromatography (4:1 hexanes/EtOAc) to give (4-Cyclohexyl-3-trifluoromethyl-phenyl)-methanol.

Provenance & Evidence