1192813-41-4

5418-51-9

1717-59-5

1192813-41-4

Step A: Synthesis of 2-(difluoromethoxy)-5-nitropyridine To a solution of 2-hydroxy-5-nitropyridine (7 g, 50 mmol) in acetonitrile (500 mL) was sequentially added anhydrous sodium sulfate (1.5 g, 10.6 mmol) and 2,2-difluoro-2-(fluorosulfonyl)acetic acid (6.2 mL, 60 mmol). The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the reaction was quenched with saturated aqueous sodium bicarbonate, followed by distillation under reduced pressure to remove the acetonitrile. The remaining aqueous phase was extracted with ethyl acetate and the organic phase was sequentially washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting light brown oily solid was ground with mixed ether/hexane solvent, and the filtrate was concentrated after filtration to afford the target product 2-(difluoromethoxy)-5-nitropyridine (4.7 g, 24.7 mmol, 49% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm: 9.14 (d, J = 2.76 Hz, 1H), 8.68 (dd, J = 9.03, 2.76 Hz, 1H), 7.98 (s, 0.5H), 7.62 (s, 0.5H), 7.34 (d, J = 9.03 Hz, 1H).