Example 3A: Synthesis of 2-chloro-5-fluoronicotinonitrile
81.2 mL (582.25 mmol) of triethylamine was added to a 783 mL dichloromethane suspension containing 46.2 g (264.66 mmol) of 2-chloro-5-fluoronicotinonitrile, and the mixture was subsequently cooled to 0°C. Under continuous stirring, 41.12 mL (291.13 mmol) of trifluoroacetic anhydride was slowly added dropwise, and after completion of the dropwise addition, the reaction mixture was kept at 0 °C with continued stirring for 1.5 hours. After completion of the reaction, the reaction mixture was washed twice with saturated aqueous sodium bicarbonate (391 mL each time), and the organic phase was dried and concentrated under reduced pressure to give the crude product. The final product was 2-chloro-5-fluoronicotinonitrile with a yield of 42.1 g and 90% yield. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ= 8.66 (dd, 1H), 8.82 (d, 1H).
