Example 4 (b) Synthesis of 5-chloro-3-fluoro-2-nitropyridine: In a 250 mL round-bottom flask, 2-amino-5-chloro-3-fluoropyridine (1.5 g, 1.46 mmol) and concentrated sulfuric acid (50 mL) were added with the stirrer installed. The mixture was stirred until completely dissolved and potassium thiosulfate (13 g, 50 mmol) was added in batches. The reaction mixture was stirred overnight, during which the color gradually changed from light green to dark yellow. After completion of the reaction, the mixture was slowly poured into 500 g of ice and stirring was continued for 10 minutes. Subsequently, solid sodium carbonate was added in batches to adjust the pH to 8-10. the products were extracted with ethyl acetate, the organic phases were combined and concentrated to dryness. The crude product was purified by column chromatography (eluent: 10-15% hexane solution of ethyl acetate) to afford 5-chloro-3-fluoro-2-nitropyridine (0.99 g, 5.6 mmol, 54% yield). The structure of the product was confirmed by 1H NMR (d6-DMSO).
