Pyridine, hydrofluoride (1:1) → HCID 178517850, compound

Temperature

0 °C

To a 25 mL round bottom flask was added 5-chloro-6-ethoxy-1,7-naphthyridin-8-amine (1.03 mmol), followed by hydrogen fluoride pyridine (5 mL). The solution was cooled to 0° C., then sodium nitrite (1.23 mmol) was added in portions. The mixture was warmed to room temperature over a period of 1 h. The reaction was then neutralized with saturated NaHCO3 and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The resultant crude residue was dissolved in dichloroethane (50 mL), then AlCl3 (820 mg, 6.18 mmol) was added in one portion. The mixture was refluxed for 2 h under Ar. The solution was allowed to cool to room temperature, then diluted with water. The aqueous phase was extracted with ethyl acetate, the organic layer was washed with brine then dried over Na2SO4. The solvent was concentrated to yield 5-chloro-8-fluoro-1,7-naphthyridin-6-ol (180 mg, 88%) as a pale yellow solid. LC/MS m/z 199 [M+H].

1. temperatureThe mixture was warmed to room temperature over a period of 1 h
2. extractionextracted with ethyl acetate
3. washThe organic layer was washed with brine
4. dry with materialdried over Na2SO4
5. concentrationconcentrated
6. dissolutionThe resultant crude residue was dissolved in dichloroethane (50 mL)
7. temperatureThe mixture was refluxed for 2 h under Ar
8. temperatureto cool to room temperature
9. extractionThe aqueous phase was extracted with ethyl acetate
10. washthe organic layer was washed with brine
11. dry with materialthen dried over Na2SO4
12. concentrationThe solvent was concentrated

ORD record

ord-9f056e73766e459ea60f54c6158f2381

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318941B2