N-bromobutanimide → 5-Bromo-3-(difluoromethoxy)pyridin-2-amine

To a solution of 3-(difluoromethoxy)pyridin-2-amine (2.3 g, 14.36 mmol) in acetonitrile (15 mL) was added N-bromosuccinimide (2.61 g, 14.65 mmol) over 3 min at 0° C. The reaction mixture was stirred at the same temperature for another 20 min and subsequently concentrated to dryness in vacuo. The resulting viscous mass was diluted with water and extracted with ethyl acetate (3×60 mL). The combined organic layers were dried over sodium sulfate and concentrated to dryness in vacuo. The resulting residue was purified by column chromatography (silica gel, 100-200 mesh, 20% ethyl acetate in hexane) affording 5-bromo-3-(difluoromethoxy)pyridin-2-amine (3.2 g, 93%): 1H NMR (400 MHz, DMSO-d6) δ 7.89 (s, 1H), 7.51 (s, 1H), 7.16 (t, J=73.6 Hz, 1H), 6.34 (s, 2H).

1. concentrationsubsequently concentrated to dryness in vacuo
2. additionThe resulting viscous mass was diluted with water
3. extractionextracted with ethyl acetate (3×60 mL)
4. dry with materialThe combined organic layers were dried over sodium sulfate
5. concentrationconcentrated to dryness in vacuo
6. customThe resulting residue was purified by column chromatography (silica gel, 100-200 mesh, 20% ethyl acetate in hexane)

ORD record

ord-9713aadb676e4ee2924cb0477bd7ee98

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365583B2