General procedure for the synthesis of 4-bromo-2-difluoromethoxypyridine from 4-bromo-2-hydroxypyridine and sodium 2-chloro-2,2-difluoroacetate:
Example 26i: 4-Bromo-2-hydroxypyridine (200 mg, 1.15 mmol) and sodium 2-chloro-2,2-difluoroacetate (210 mg, 1.38 mmol) were suspended in dry acetonitrile (8 mL). The reaction mixture was heated to reflux overnight and subsequently cooled to room temperature. The reaction mixture was extracted directly with pentane (3 × 5 mL). The organic phases were combined and concentrated to afford 219 mg (85% yield) of 4-bromo-2-difluoromethoxypyridine. Product characterization data were as follows: 1H-NMR (500 MHz, DMSO-d6) δ 8.18 (d, 1H), 7.70 (t, 1H), 7.56 (d, 1H), 7.50 (s, 1H); mass spectra (CI+) m/z 226, 224 [M + 1]+.
