N-Bromosuccinamide → 5-Bromo-3-(difluoromethoxy)pyridin-2-amine
反応式
[Br:1]NC(=O)CCC(N)=O.[F:10][CH:11]([F:20])[O:12][C:13]1[C:14]([NH2:19])=[N:15][CH:16]=[CH:17][CH:18]=1>C(#N)C>[Br:1][C:17]1[CH:18]=[C:13]([O:12][CH:11]([F:10])[F:20])[C:14]([NH2:19])=[N:15][CH:16]=1参加物
4
反応条件
- 温度
- 0 °C
実験手順
N-Bromosuccinamide (1.00 g, 5.62 mmol) was added portionwise over 10 min to a cooled solution of 3-(difluoromethoxy)pyridin-2-amine (1.12 g) in dry acetonitrile (20 ml) at 0° C. The reaction mixture was further stirred at 0° C. for 10 min. The mixture was concentrated, and residue was partitioned between EtOAc/sat. Na2CO3/H2O (30 ml/15 ml/15 ml). The organic phase was sequentially washed with sat. aqueous Na2CO3/H2O (15 ml/15 ml) and brine (30 ml), dried (Na2SO4), and concentrated. The resulting residue was extracted with EtOAc/hexanes (6 ml/30 ml), and the resulting suspension was filtered through Celite, and the resulting filtrate was concentrated to provide 1.32 g (80%) of 5-bromo-3-(difluoromethoxy)pyridine-2-amine. LCMS (m/z, MH+): 238.9, tR=0.52 min; 1H NMR (CDCl3, 400 MHz) δ 7.99 (d, J=2.0 Hz, 1H), 7.41 (m, 1H), 6.50 (t, J=72.8 Hz, 1H), 4.75 (br s, 2H).