Methanol → [2-Bromo-6-(trifluoromethoxy)phenyl]methanol

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Reaction Steps

To a stirred solution of 2-bromo-6-[(trifluoromethyl)oxy]benzoic acid (1.116 g, 3.92 mmol, Parkway Scientific), in THF (45 ml), under nitrogen, was added 1.0 M borane-tetrahydrofuran complex (12 ml, 12 mmol) carefully over about 2 minutes. The solution was then heated at gentle reflux for 24 h and allowed to cool. Methanol (20 ml) was added dropwise. The solution was heated at reflux for 30 min and allowed to cool. The solvent was evaporated in vacuo and acidified with dilute aqueous HCl. The mixture was extracted with chloroform and then filtered through a hydrophobic frit. The chloroform was evaporated in vacuo to give {2-bromo-6-[(trifluoromethyl)oxy]phenyl}methanol as a colourless oil (1.07 g). {2-bromo-6-[(trifluoromethyl)oxy]phenyl}methanol (1.06 g, 3.91 mmol) in dichloromethane (14 ml) under nitrogen was stirred and cooled to −10° C. A solution of phosphorus tribromide (0.37 ml, 3.91 mmol) in DCM (3.5 ml) was then added dropwise over about 12 min. The temperature was allowed to rise to ambient temperature over about 3 h then stirred for a further 2 h. Saturated aqueous sodium bicarbonate (12 ml) was then added in portions with stirring and the mixture left in a fridge over weekend. The mixture was extracted into chloroform three times. The combined chloroform extracts were filtered through a hydrophobic frit and the solvent was evaporated in vacuo to give 1-bromo-2-(bromomethyl)-3-[(trifluoromethyl)oxy]benzene as a colourless oil (0.6 g).

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