General procedure for the synthesis of 3-(difluoromethoxy)pyridin-2-amine from 3-(difluoromethoxy)-2-nitropyridine: 3-(difluoromethoxy)-2-nitropyridine (450 mg, 2.37 mmol) was dissolved in a mixed solvent of ethanol (2 mL) and acetic acid (2 mL) and reduced iron powder (397 mg, 7.10 mmol) was added. The reaction mixture was stirred at 100 °C overnight. Since the ingredients were not fully reacted, reduced iron powder (397 mg, 7.10 mmol) was added again and stirring was continued at 100 °C overnight. After completion of the reaction, the mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. To the concentrated residue was added saturated aqueous sodium bicarbonate and extracted three times with ethyl acetate. The organic layers were combined, dried with anhydrous magnesium sulfate, filtered and purified by silica gel column chromatography (eluent: chloroform/methanol=9/1, v/v) to afford the target product 3-(difluoromethoxy)pyridin-2-amine (250 mg, 66% yield). The product was detected by electrospray ionization mass spectrometry (ESIMS), m/z: 161 (M + H)+; 1H NMR (270 MHz, CDCl3, δ): 4.79 (broad single peak, 2H), 6.14-6.80 (multiple peaks, 2H), 7.19-7.35 (multiple peaks, 1H), 7.85-7.98 (multiple peaks, 1H).
