General procedure for the synthesis of 2-methoxy-6-methylpyrazine from 2-chloro-6-methylpyrazine: 2-chloro-6-methylpyrazine (24 g, 186.7 mmol) was suspended in anhydrous methanol (240 mL) under the protection of nitrogen followed by the addition of sodium methanolate (12.1 g, 224 mmol). The reaction mixture was stirred at 60-70°C for 16 hours. After completion of the reaction, the mixture was cooled to room temperature and filtered to remove insoluble material. The filtrate was concentrated under reduced pressure to give 2-methoxy-6-methylpyrazine (22 g, 95% yield). The product was characterized by 1H NMR (CDCl3, 400 MHz): δ 7.98 (s, 1H), 7.94 (s, 1H), 3.91 (s, 3H), 3.40 (s, 3H). LC-MS analysis showed a retention time tR = 1.47 min (Method 14) and a mass-to-charge ratio of m/z = 124.8 [M + H]+.
