Ethyl Acetate → 2-Chloro-4-ethoxypyridine

Temperature

25 °C

To a mixture of 2-chloro-4-nitropyridine (170 g, 1070 mmol) in THF (2 L) was added sodium ethanolate (109.45 g, 1610 mmol) slowly at 0° C. The mixture was stirred at 25° C. for 12 h. LCMS and TLC (PE/EA=5:1, Rf=0.6) showed the reaction was finished. The mixture was filtered, and most solvent of the filtrate was removed in vacuo. The residue was extracted with EA (800 mL×3), and the organic layer was washed with saturated NaCl solution (1 L), dried over Na2SO4, filtered, and concentrated to give crude 2-chloro-4-ethoxypyridine (157 g, 1.0 mol, 92% yield) as a solid: 1H NMR (400 MHz, CD3OD) δ 8.15 (d, J=6.0 Hz, 1H), 6.99 (d, J=2.0 Hz, 1H), 6.91-6.89 (m, 1H), 4.16-4.14 (m, 2H), 1.41-1.38 (m, 3H); ES-LCMS m/z 158 (M+H).

1. filtrationThe mixture was filtered
2. custommost solvent of the filtrate was removed in vacuo
3. extractionThe residue was extracted with EA (800 mL×3)
4. washthe organic layer was washed with saturated NaCl solution (1 L)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated

ORD record

ord-d0c27e869295489692c07a976fe8dc04

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09382238B2