5-Bromo-3-fluoro-2-(hydroxymethyl)pyridine

1211538-72-5

1206968-92-4

The general procedure for the synthesis of (5-bromo-3-fluoropyridin-2-yl)methanol using 5-bromo-3-fluoro-2-pyridinecarboxylic acid methyl ester as starting material was as follows: 5-bromo-3-fluoro-2-pyridinecarboxylic acid methyl ester (12.82 mmol) was dissolved in anhydrous ethanol (50.0 mL), followed by addition of sodium borohydride (64.1 mmol). The resulting suspension was heated to reflux and the reaction was maintained for 4 hours and then cooled to room temperature. The reaction mixture was concentrated under reduced pressure to remove the solvent and the residue was diluted with a mixture of saturated aqueous sodium bicarbonate and brine and subsequently extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered and silica gel powder (about 3 g) was added and evaporated to dryness under reduced pressure. Purification by silica gel column chromatography (eluent: 10% ethyl acetate solution of hexane) afforded the target product (5-bromo-3-fluoropyridin-2-yl)methanol (2.27 g, 82% yield) as a white solid. Mass spectrum (electrospray ionization, positive ion mode) m/z: 205.9, 207.7 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm: 4.55 (dd, J = 6.06, 2.27 Hz, 2H), 5.40 (t, J = 6.06 Hz, 1H), 8.15 (dd, J = 9.35, 1.77 Hz, 1H), 8.52-8.57 (m, 1H).