General procedure for the synthesis of 2-chloro-5-nitroisonicotinic acid from 2-chloro-5-nitro-4-methylpyridine: 2-chloro-4-methyl-5-nitropyridine (31 g, 180 mmol) was dissolved in concentrated hydrochloric acid (300 mL) and the resulting mixture was cooled to 0 °C. Subsequently, chromium trioxide (CrO3, 59.4 g, 594 mmol) was slowly added to the solution. After continuous stirring at 0 °C for 1 h, the reaction mixture was gradually warmed to room temperature and stirring was continued overnight. After completion of the reaction, the mixture was slowly poured into ice water (1 L). After the mixture was warmed up to room temperature, filtration operation was carried out. The resulting solid was washed thoroughly with distilled water (2 L) and subsequently dried under vacuum to afford the target product 2-chloro-5-nitroisonicotinic acid as a white solid (28.5 g, 78% yield). The product was analyzed by LC/MS showing MS (ES) m/e 203 (MH+); 1H NMR (300 MHz, DMSO-d6) δ ppm 8.04 (s, 1H), 9.16 (s, 1H).
