Hydrochloric Acid → (2,6-Dichloro-4-(trifluoromethyl)phenyl)methanol

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Reaction Conditions

Reaction Steps

The required [2,6-dichloro-4-(trifluoromethyl)-phenyl]nethanol was prepared as follows: To a solution of 1,3-dichloro-5-(trifluoromethyl)benzene (4.73 g; 22 mmol) in THF (40 mL) was added n-BuLi in hexanes (8 mL; 2.50 mol/1; 20 mmol), at −78° C. The resulting mixture was stirred for 15 minutes and poured onto dry ice in THF. The reaction mixture was acified to pH=3 (with 5 M aqueous HCl solution) and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, CH2Cl2/MeOH 8:2) to afford 2,6-dichloro-4-(trifluoromethyl)benzoic acid (1.2 g). To a solution of this 2,6-dichloro-4-(trifluoromethyl)benzoic acid (1.7 g; 6.6 mmol) in THF (20 mL) was added dropwise a solution of borane-THF complex in THF (1 mol/1, 13.3 mL; 13.3 mmol). Subsequently, the resulting mixture was stirred overnight at 60° C. To the reaction mixture was added 1 M aqueous HCl (30 mL), at 0° C., and the resulting mixture was stirred at RT for 10 minutes. The resulting mixture was concentrated in vacuo and the residue was partitioned between EtOAc and 5% aqueous NaHCO3-solution. The layers were separated and the organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, Et2O:hexanes 1:3 followed by Et2O:hexanes 1:1) to afford [2,6-dichloro-4-(trifluoromethyl)phenyl]-methanol (1.3 g), which was used as such in the next step.

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