5-Aminoquinoline → 5-Fluoroquinoline

To a suspension of 5-aminoquinoline (10.0 g, 0.069 mol) in 48% HBF4 (40 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 (50 mL). The resulting suspension was filtered and the solid dried. This solid was added portionwise to refluxing xylene (80 mL) and stirred for 2 hours then allowed to cool. The xylene was decanted off and the residue was dissolved in 1N aqueous hydrochloric acid (100 mL). After neutralization with sodium carbonate, the mixture was extracted with ethyl acetate (3×80 mL). The extracts were dried over sodium sulfate, filtered and the volatiles were removed in vacuo. The residue was purified by silica gel column chromatography, eluting with 2% ethyl acetate in petroleum ether to afford 5-fluoroquinoline as a colorless oil (2.5 g, 24.5%).

1. filtrationThe resulting suspension was filtered
2. customthe solid dried
3. additionThis solid was added portionwise
4. temperatureto refluxing xylene (80 mL)
5. stirringstirred for 2 hours
6. temperatureto cool
7. customThe xylene was decanted off
8. dissolutionthe residue was dissolved in 1N aqueous hydrochloric acid (100 mL)
9. extractionAfter neutralization with sodium carbonate, the mixture was extracted with ethyl acetate (3×80 mL)
10. dry with materialThe extracts were dried over sodium sulfate
11. filtrationfiltered
12. customthe volatiles were removed in vacuo
13. customThe residue was purified by silica gel column chromatography
14. washeluting with 2% ethyl acetate in petroleum ether

ORD record

ord-0f134b830b5044f38339458e86bb2c05

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073902B2