反应详情

8-Fluoroquinolin-2(1H)-one (26 g, 159 mmol) was slurried phosphoryl trichloride (163 mL, 1753 mmol, 11 eq) and heated to 125 for 2 h. The reaction was cooled to rt and poured onto 1.2 L of ice water with vigorous stirring. When mixture had cooled to rt, the orange solid was filtered and washed with water and dried under vacuum overnight to afford 27 g of crude material. The crude material was recrystallized from hexanes by dissolving in ˜700 mL of hexanes at reflux and decanting away from residual tar. The hexane solution was cooled to 0° C. and the precipitate 2-chloro-8-fluoroquinoline was filtered. The mother liquor was concentrated in vacuo and recrystallized from hexanes to obtain a second crop of 2-chloro-8-fluoroquinoline. 1H NMR (400 MHz, CDCl3) δ ppm 8.14 (dd, J=8.6, 1.2 Hz, 1H), 7.62 (br d, 1H), 7.52 (td, J=7.8, 4.7 Hz, 1H), 7.45 (m, 2H).

1. temperatureheated to 125 for 2 h
2. temperatureWhen mixture had cooled to rt
3. filtrationthe orange solid was filtered
4. washwashed with water
5. customdried under vacuum overnight
6. customto afford 27 g of crude material
7. customThe crude material was recrystallized from hexanes
8. dissolutionby dissolving in ˜700 mL of hexanes
9. temperatureat reflux
10. customdecanting away from residual tar
11. temperatureThe hexane solution was cooled to 0° C.
12. filtrationthe precipitate 2-chloro-8-fluoroquinoline was filtered
13. concentrationThe mother liquor was concentrated in vacuo
14. customrecrystallized from hexanes