General procedure for the synthesis of 2-chloro-3-trifluoromethyl-5-nitropyridine from 2-hydroxy-5-nitro-3-trifluoromethylpyridine: Thionyl chloride (SOCl2, 18.45 mL, 253 mmol) was slowly added dropwise to a reaction vial containing 5-nitro-3-(trifluoromethyl)pyridin-2-ol (2.63 g, 12.64 mmol). Subsequently, N,N-dimethylformamide (DMF, 1.957 mL, 25.3 mmol) was added as a catalyst. The reaction mixture was stirred at 100°C for 10 hours. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure to remove excess thionyl chloride. The concentrated residue was extracted by partitioning between ethyl acetate (EA) and saturated sodium bicarbonate (NaHCO3) solution. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure to afford the crude product 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (2.46 g, 10.86 mmol, 86% yield), which could be used in the next reaction without further purification. Thin layer chromatography (TLC) analysis conditions: petroleum ether/ethyl acetate (PE/EA = 5:1), Rf = 0.6. 1H NMR (400 MHz, CDCl3) δ: 9.23-9.59 (m, 1H), 8.79 (d, J = 2.4 Hz, 1H).
