Borane;tetrahydrofuran → 3-Chloro-4-(hydroxymethyl)phenol

To a solution of 2-chloro-4-hydroxybenzoic acid hydrate (5.0 g, 26.2 mmol, Acros) in THF (80 ml) was added dropwise 1 M borane-tetrahydrofuran complex (50 ml, 50 mmol, Aldrich) at ambient temperature under nitrogen. The resulting suspension was stirred at ambient temperature for 20 min and then heated to 80° C. for 1.5 h. To the reaction at ambient temperature was added a further amount of 1 M borane-tetrahydrofuran (20 ml, 20 mmol) and the suspension heated to 80° C. for 1 h. The solution was allowed to cool to ambient temperature and then carefully quenched by dropwise addition of methanol (40 ml). The solution was heated to 80° C. for 40 min. The solvent was removed in vacuo and the residue applied to a 50 g aminopropyl cartridge (pre-washed with methanol). The cartridge was eluted with methanol and the combined methanol fractions concentrated in vacuo to leave a white solid (4.58 g). A portion of the semi-crude material (1.5 g) was pre-absorbed on florosil and purified on silica (100 g) using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white solid (0.92 g); LCMS: (System 4) (M-H)−=157, tRET=1.29 min.