5-Aminoquinoline → 5-Fluoroquinoline

To a solution of quinolin-5-amine (2 g, 13.9 mmol) in 10 mL of 48% HBF4 at 0° C. was added sodium nitrite (933 mg, 13.5 mmol) portionwise. This was stirred for 1 hour and then poured into 1:1 ethyl acetate diethyl ether mixture (50 mL). The resulting suspension was filtered and the solid was dried. This solid was added portionwise to refluxing xylene (30 mL) and stirred for 3 hours, then allowed to cool. The xylene was decanted off and the residue was dissolved in 1N HCl (50 mL). After neutralization with NaHCO3, the mixture was extracted with ethyl acetate (3×50 mL). The extracts were dried over sodium sulfate, filtered and the volatiles were removed under reduced pressure. The residue was purified by silica gel chromatography (3% EtOAc/PE) to afford 800 mg of title compound as colorless oil. LC-MS: m/z 148.2 (M+H)+

1. filtrationThe resulting suspension was filtered
2. customthe solid was dried
3. additionThis solid was added portionwise
4. temperatureto refluxing xylene (30 mL)
5. stirringstirred for 3 hours
6. temperatureto cool
7. customThe xylene was decanted off
8. dissolutionthe residue was dissolved in 1N HCl (50 mL)
9. extractionAfter neutralization with NaHCO3, the mixture was extracted with ethyl acetate (3×50 mL)
10. dry with materialThe extracts were dried over sodium sulfate
11. filtrationfiltered
12. customthe volatiles were removed under reduced pressure
13. customThe residue was purified by silica gel chromatography (3% EtOAc/PE)

ORD record

ord-bf0b01f0883e4332b486cbd2900c7ddb

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09108921B2