The general procedure for the synthesis of 2-hydroxy-3-nitro-5-trifluoromethylpyridine using 2-hydroxy-5-trifluoromethylpyridine as starting material was as follows: 2-hydroxy-5-trifluoromethylpyridine (10.0 g, 61.3 mmol) was dissolved in concentrated sulfuric acid (50 mL), and the reaction system was cooled to 0 °C. Fuming nitric acid (14 mL, 92 mmol) was slowly added dropwise at 0 °C. After the dropwise addition, the reaction was kept at 0 °C and continued to be stirred for 1 h. Subsequently, the temperature of the reaction was raised to 65 °C and the reaction was continued to be stirred for 24 h. The reaction temperature was increased to 65 °C and the reaction was continued to be stirred. After completion of the reaction, the reaction system was cooled to room temperature and the reaction was quenched by slowly pouring into ice (300 g). Subsequently, 50% aqueous sodium hydroxide solution (85 mL) was slowly added to neutralize the reaction mixture. The aqueous phase was extracted several times with ethyl acetate (4 x 200 mL), all organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give a yellow solid 2-hydroxy-3-nitro-5-trifluoromethylpyridine 7.4 g in 58% yield. The product was characterized by 1H NMR (CDCl3): δ 8.66 (s, 1H), 8.29 (s, 1H).
