Step B: Synthesis of 6-(difluoromethoxy)pyridin-3-amine
To degassed methanol (100 mL) was added 2-(difluoromethoxy)-5-nitropyridine (4.7 g, 24.7 mmol) and 10% palladium-carbon catalyst (500 mg, 0.47 mmol). The hydrogenation reaction was carried out at atmospheric pressure for 1 hour. Upon completion of the reaction, acetic acid (2.83 mL, 49.4 mmol) was added, followed by filtration of the reaction mixture through diatomaceous earth and concentration of the filtrate in vacuum to afford 6-(difluoromethoxy)pyridin-3-amine (6.33 g, 25.9 mmol, 105% yield) as an olive green liquid product.
1H NMR (400 MHz, MeOD-d4) δ ppm: 7.60 (d, J = 2.76 Hz, 1H), 7.37 (s, 0.5H), 7.15 (dd, J = 8.66, 2.89 Hz, 1H), 7.00 (s, 0.5H), 6.71 (d, J = 8.78 Hz, 1H).
