O-Xylene → 5-Fluoroquinoline

To a suspension of 5-aminoquinoline (50 g, 347 mmol) in 48% HBF4 (200 mL) at 0° C. was added portionwise sodium nitrite. This was stirred for 1 hour and then poured into 1:1 ethyl acetate/diethyl ether (500 mL). The resulting suspension was filtered and the solid dried. This solid (82.5 g, 338 mmol) was added portionwise to refluxing xylene (1 L) and stirred for 2 hours then allowed to cool. The xylene was decanted off and the residue dissolved in 1N hydrochloric acid (600 mL). After neutralization with sodium carbonate, the mixture was extracted with ethyl acetate (10×500 mL). The extracts were dried over sodium sulfate, filtered and the volatiles removed under reduced pressure. The residue was subjected to silica gel chromatography, eluting with 10-20% diethyl ether in hexanes. Fractions containing product were combined and concentrated under reduced pressure to provide 28.1 g (55%) of the desired compound.

1. filtrationThe resulting suspension was filtered
2. customthe solid dried
3. stirringstirred for 2 hours
4. temperatureto cool
5. customThe xylene was decanted off
6. dissolutionthe residue dissolved in 1N hydrochloric acid (600 mL)
7. extractionAfter neutralization with sodium carbonate, the mixture was extracted with ethyl acetate (10×500 mL)
8. dry with materialThe extracts were dried over sodium sulfate
9. filtrationfiltered
10. customthe volatiles removed under reduced pressure
11. washeluting with 10-20% diethyl ether in hexanes
12. additionFractions containing product
13. concentrationconcentrated under reduced pressure

ORD record

ord-bfe158d5f94e4e94b4f8cccad40e7524

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06743785B2