Methanol → 4-Phenoxy-2-(trifluoromethyl)benzenemethanol

To a stirred solution of 4-(phenyloxy)-2-(trifluoromethyl)benzoic acid (for a preparation see Intermediate 35)(0.507 g, 1.80 mmol), in THF (40 ml), under nitrogen, was added borane-tetrahydrofuran complex (0.463 g, 5.39 mmol, Aldrich) carefully over about 2 min. The solution was stirred for 40 min at ambient temperature and then heated at gentle reflux for 20 h. To the mixture at ambient temperature was added methanol (10 ml) dropwise and then the solution was heated to reflux for 30 min. The solvent was evaporated in vacuo and the residue acidified with dilute aqueous HCl. The mixture was extracted with chloroform and the phases separated using a hydrophobic frit. The solvent was evaporated in vacuo to leave [4-(phenyloxy)-2-(trifluoromethyl)phenyl]methanol as a colourless oil (0.491 g). [4-(phenyloxy)-2-(trifluoromethyl)phenyl]methanol (0.491 g, 1.83 mmol) in dichloromethane (10 ml) under nitrogen was stirred and cooled to −5° C. A solution of phosphorus tribromide (0.173 ml, 1.831 mmol) in DCM (3.5 ml) was then added dropwise over about 10 min. The solution was then allowed to warm to room temperature and stirred for 4 h. A saturated solution of aqueous sodium bicarbonate (10 ml) was then added and the mixture stirred vigorously. The emulsion was further diluted with water and chloroform. The phases were separated using a hydrophobic frit. The aqueous phase was further extracted with chloroform. The combined organic extracts were dried (Na2SO4) and filtered. The filtrate was re-dried with (MgSO4), filtered and the solvent removed in vacuo to give 4-(bromomethyl)-3-(trifluoromethyl)phenyl ether as a colourless oil (0.518 g).