O-Xylene → 5-Fluoroquinoline

Participants

Reaction Steps

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.

Provenance & Evidence