反应详情

温度

60 °C

3-fluoro-4-nitrophenol (200.0 g, 1.27 mol) was added to a solution of 2-(chloromethyl)-5-methylpyridine hydrochloride (222 g, 1.25 mol), powdered potassium carbonate (383.6 g, 2.75 mol), potassium iodide (207 g, 1.25 mol), and acetonitrile (3.4 L). The resulting mixture was stirred at 60° Celsius for 2 h. The reaction was cooled to RT, concentrated to dryness and partitioned between H2O (1.5 L) and ethyl acetate (1.5 L). The organic layers were separated and the aqueous layer was extracted with ethyl acetate (1.0 L). The combined organic layers were washed with brine (1 L) then dried over magnesium sulfate, filtered, and concentrated to dryness. The crude solid was recrystallized from i-PrOH (1.5 L) at 70° Celsius. After cooling to 0° Celsius the solid was collected by filtration and rinsed with i-PrOH (2×200 mL) and heptanes (2×200 mL) to yield the title compound as a dark solid (242.0 g, 73.9%). MS (ESI): mass calcd. for C13H11FN2O3, 262.10; m/z found, 263.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.44 (s, 1H), 8.16 (t, J=9.2, 1H), 7.76-7.62 (m, 1H), 7.45 (d, J=7.9, 1H), 7.30 (dd, J=13.7, 2.5, 1H), 7.07 (dd, J=9.3, 1.9, 1H), 5.30 (s, 2H), 2.31 (s, 3H).

1. temperatureThe reaction was cooled to RT
2. concentrationconcentrated to dryness
3. custompartitioned between H2O (1.5 L) and ethyl acetate (1.5 L)
4. customThe organic layers were separated
5. extractionthe aqueous layer was extracted with ethyl acetate (1.0 L)
6. washThe combined organic layers were washed with brine (1 L)
7. dry with materialthen dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated to dryness
10. customThe crude solid was recrystallized from i-PrOH (1.5 L) at 70° Celsius
11. temperatureAfter cooling to 0° Celsius the solid
12. filtrationwas collected by filtration
13. washrinsed with i-PrOH (2×200 mL) and heptanes (2×200 mL)