反应详情

温度

80 °C

To a suspension of N-(4-(2,5-difluoro-4-nitrophenoxy)pyridin-2-yl)propionamide (27.2 g, 84.2 mmol) in EtOH (750 mL) was added a solution of NH4Cl (18 g, 337 mmol) in water (188 mL) and Fe powder (97%, 325 mesh, 18.8 g, 337 mmol) in one portion at RT. The mixture was then heated at 80° C. for 1 h, cooled to ambient temp, filtered through a bed of diatomaceous earth, and washed with MeOH (1 L). The combined filtrates were concentrated to dryness and purified by silica gel chromatography (EtOAc/hexanes) to give N-(4-(4-amino-2,5-difluorophenoxy)pyridin-2-yl)propionamide (17.4 g, 70.5% yield). 1H-NMR (400 MHz, CDCl3): δ 8.07 (d, J=5.6 Hz, 1 H), 8.00 (br s, 1 H), 7.77 (d, J=2 Hz, 1 H), 6.85 (dd, J=10.4, 7.2 Hz, 1 H), 6.63-6.58 (m, 2 H), 3.79 (s, 2 H), 2.38 (q, J=7.6 Hz, 2 H), 1.20 (t, J=7.6 Hz, 3H); MS (ESI): m/z 294.1 (M+H+).

1. temperaturecooled to ambient temp
2. filtrationfiltered through a bed of diatomaceous earth
3. washwashed with MeOH (1 L)
4. concentrationThe combined filtrates were concentrated to dryness
5. custompurified by silica gel chromatography (EtOAc/hexanes)