To a stirred solution of 2-hydroxy-4-methylpyridine (10 g, 92 mmol) in chloroform (350 mL) was sequentially added silver carbonate (34.2 g, 124 mmol) and iodomethane (130 g, 920 mmol) at room temperature. The reaction mixture was stirred continuously under light-avoidance conditions for 48 hours. After completion of the reaction, the reaction mixture was filtered through diatomaceous earth and the filter cake was washed with ether. The filtrate was concentrated at a temperature below 20 °C and the resulting residue was purified by column chromatography using n-pentane/ether (5:1, v/v) as eluent to afford 2-methoxy-4-methylpyridine (8.0 g, 71% yield) as a colorless oil. The structure of the product was characterized by 1H NMR (CDCl3, δ): 8.02 (d, 1H, J=5.4 Hz), 6.69 (d, 1H, J=5.4 Hz), 6.55 (s, 1H), 3.91 (s, 3H), 2.28 (s, 3H); 13C NMR (CDCl3, δ): 164.40, 149.72, 146.31. 118.21, 110.88, 53.17, 20.81; Mass Spectrometry (MS) m/z (relative abundance): 123 (M+, 76%), 122 (100%) confirmed.
