General procedure for the synthesis of (2-chloro-6-methoxypyridin-4-yl)methanol from 2-chloro-6-methoxyisonicotinic acid: Borane-tetrahydrofuran complex (1.0 M tetrahydrofuran solution, 40 ml) was slowly added dropwise to an anhydrous solution of 2-chloro-6-methoxyisonicotinic acid (2.5 g) in anhydrous tetrahydrofuran (50 ml) at 0°C and under nitrogen protection. The titration process lasted for 15 minutes. After completion of the dropwise addition, the cooling bath was removed and the reaction mixture was allowed to warm up gradually to room temperature. After 3 hours of reaction, the mixture was again cooled to 0°C and borane-tetrahydrofuran complex (1.0 M tetrahydrofuran solution, 40 ml) was added dropwise over 15 minutes. After completion of the dropwise addition, the cooling bath was removed and the mixture was warmed to room temperature and stirred continuously for 17 hours. After completion of the reaction, the mixture was cooled to 0°C and the reaction was quenched with 1.0 M aqueous sodium hydroxide solution (30 ml) and subsequently diluted with saturated aqueous ammonium chloride solution (50 ml). The reaction mixture was extracted with ether (2 x 100 ml) and the organic layers were combined. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was ground with hexane and filtered to give (2-chloro-6-methoxypyridin-4-yl)methanol (2.0 g) as a white solid.LCMS: Rt 1.16 min, m/z 174/176 [M+H]+.1H-NMR (400 MHz, CDCl3) δ (ppm): 1.96 (t, 1H), 3.94 (s, 3H). 4.67 (d, J=3.67Hz, 2H), 6.65 (d, J=0.86Hz, 1H), 6.91 (s, 1H).
