Synthesis of 6-chloro-4-methoxy-3-cyanopyridine (2): to a solution of 4,6-dichloronicotinonitrile (1) (200 mg, 1.06 mmol) in anhydrous methanol (10 mL) was added sodium methanol solution (0.5 M in MeOH, 2.12 mL, 1.06 mmol). The reaction mixture was stirred at 60 °C overnight. After completion of the reaction, the mixture was cooled to room temperature and neutralized by addition of hydrochloric acid (1 M, 8 mL). Subsequently, the volatile components were removed by distillation under reduced pressure. The product was purified by a Biotage fast chromatography system (elution gradient: 10%-50% ethyl acetate/hexane) to afford 6-chloro-4-methoxy-3-cyanopyridine (150 mg, 77% yield). The structure of the product was confirmed by 1H NMR (400 MHz, chloroform-d): δ 8.48 (s, 1H), 6.98 (s, 1H), 4.03 (s, 3H).
