General procedure for the synthesis of 2-bromo-3-(difluoromethoxy)pyridine from 2-bromo-3-hydroxypyridine and sodium difluorochloroacetate: 2-bromo-3-hydroxypyridine (3.55 g, 20.4 mmol), sodium difluorochloroacetate (6.22 g, 40.8 mmol), and sodium hydroxide (0.90 g, 22.4 mmol) were reacted with 2-bromo-3-hydroxypyridine (3.55 g, 20.4 mmol), sodium difluorochloroacetate (6.22 g, 40.8 mmol), and sodium hydroxide (0.90 g, 22.4 mmol) in a N,N-dimethylformamide (20 mL) in N,N-dimethylformamide (20 mL) was heated and reacted at 55 °C for 111 hours. After completion of the reaction, it was cooled to room temperature and concentrated under reduced pressure. The resulting residue was partitioned between ethyl acetate (80 mL) and saturated sodium bicarbonate solution (40 mL). The organic phase was separated, washed with saturated saline (40 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (eluent: 100:0 to 0:100 hexane-ethyl acetate gradient) to afford 2-bromo-3-(difluoromethoxy)pyridine 1.95 g (43% yield). Product characterization data: LCMS (m/z, MH+): 225.9, tR = 0.74 min; 1H NMR (CDCl3, 400 MHz) δ 8.23-8.33 (m, 1H), 7.52-7.60 (m, 1H), 7.27-7.35 (m, 1H), 6.60 (t, J = 72.4 Hz, 1H).
