反应详情

温度

45 °C

To a solution of 3-bromo-5-ethoxypyridine-1-oxide (40 g, 183 mmol) in DCM (200 mL) at 0° C. was slowly added POCl3 (159 mL, 1701 mmol) over 30 min. Then the resulting solution was warmed to 45° C. and stirred for 15 h. The mixture was concentrated and adjusted pH=9-10 with 10% NaOH solution, extracted with DCM (300 mL×2), dried over Na2SO4, filtered, and concentrated to give the crude product which was purified by silica column chromatography (10% EA: 90% PE, 800 g silica column). All fractions found to contain product by TLC (EA: PE=1:5, Rf=0.6) were combined and concentrated to yield an oil of 5-bromo-2-chloro-3-ethoxypyridine (30 g, 60.9 mmol, 33% yield): 1H NMR (400 MHz, CD3OD) δ 8.00-7.99 (d, J=2.0 Hz, 1H), 7.65-7.64 (d, J=2.0 Hz, 1H), 4.17-4.12 (m, 2H), 1.44 (t, J=7.0 Hz, 2H); ES-LCMS m/z 235 (M+H).

1. customat 0° C.
2. customover 30 min
3. concentrationThe mixture was concentrated
4. extractionadjusted pH=9-10 with 10% NaOH solution, extracted with DCM (300 mL×2)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto give the crude product which
9. customwas purified by silica column chromatography (10% EA: 90% PE, 800 g silica column)
10. concentrationconcentrated