反应详情

温度

100 °C

Phosphorus oxybromide (19 g, 0.066 mole), 7-chloro-8-fluoro-2-phenyl-1H-quinolin-4-one (6.2 g, 0.022 mole) and acetonitrile (40 mL) were combined in a 150 mL pressure bottle with a magnetic stir bar. The flask was heated at 100° C. and stirred overnight. Heat was removed, and an ice-water bath was installed. After 10 minutes, the bottle was opened, and water (60 mL) was added to the cooled stirring reaction. The quenching was exothermic to ca. 50° C. After stirring 10 minutes, a nice, filterable solid had formed, however, the reaction was extracted with 100 mL, then 3×50 mL methylene chloride. The extracts were combined, washed with saturated sodium bicarbonate solution (100 mL), and suction filtered through a small pad of silica gel, rinsing with methylene chloride. The filtrate was concentrated in vacuo, and put under high vacuum at 45° C. for 1 h to afford the crude product, which was recrystallized from 100 mL of ethanol, suction filtered to collect, and washed with ethanol. The purified product was vacuum oven dried for 1 h at 45° C. to afford the title compound as a white solid. A second crop was taken. The mother liquor was concentrated then chromatographed on silica gel with hexanes/methylene chloride 1:1 and combined with the second crop to afford additional material; 1H NMR (CDCl3, 400 MHz) δ 7.49-7.55 (m, 4H), 7.87-7.90 (dd, 1H, J=1.7 Hz & J=8.9Hz), 8.15-8.18 (dd, 2H, J=1.5 Hz & J=7.9 Hz), 8.21 (s, 1H); HPLC tR=4.15 min (OpenLynx, nonpolar—5 min).

1. temperatureHeat
2. customwas removed
3. customan ice-water bath was installed
4. waitAfter 10 minutes
5. additionwater (60 mL) was added to the cooled
6. stirringstirring
7. customreaction
8. customwas exothermic to ca. 50° C
9. stirringAfter stirring 10 minutes
10. customa nice, filterable solid had formed
11. extractionhowever, the reaction was extracted with 100 mL
12. washwashed with saturated sodium bicarbonate solution (100 mL), and suction
13. filtrationfiltered through a small pad of silica gel
14. washrinsing with methylene chloride
15. concentrationThe filtrate was concentrated in vacuo
16. waitput under high vacuum at 45° C. for 1 h
17. customto afford the crude product, which
18. customwas recrystallized from 100 mL of ethanol, suction
19. filtrationfiltered
20. customto collect
21. washwashed with ethanol
22. customdried for 1 h at 45° C.