N-bromobutanimide → 5-Bromo-3-(difluoromethoxy)pyridin-2-amine
Reaction equation
[F:1][CH:2]([F:11])[O:3][C:4]1[C:5]([NH2:10])=[N:6][CH:7]=[CH:8][CH:9]=1.[Br:12]N1C(=O)CCC1=O>C(#N)C>[Br:12][C:8]1[CH:9]=[C:4]([O:3][CH:2]([F:1])[F:11])[C:5]([NH2:10])=[N:6][CH:7]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
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).