反应详情

温度

0 °C

A solution of n-butyllithium (77 mL, 2.5 M in hexane, 0.19 mol) was added to a solution of N,N-diisopropylamine (27 mL, 0.19 mol) in dry THF (400 mL) under an atmosphere of nitrogen at −78° C. After the addition, the mixture was warmed to 0° C. for 15 minutes and then cooled again to −78° C. 2-Fluoropyridine (15.0 mL, 0.174 mol) was added dropwise to the mixture and stirred at −78° C. After 45 minutes, a pale yellow precipitate formed. N,N-Dimethylformamide (27 mL, 0.35 mol) was added slowly via syringe maintaining temperature below −55° C. After ten minutes, the cooling bath was removed and the mixture slowly warmed to room temperature. The reaction was quenched with NH4Cl/H2O and then 4 M HCl to adjust the pH ˜7. NaHCO3/H2O was then added to adjust the pH 9-10, and then extracted three times with Et2O. The combined extracts were washed with brine, dried over MgSO4, filtered and concentrated to a yellow oil. The residue was purified by chromatography on silica gel, eluting with 25% EtOAc/hexane to provide 2-fluoronicotinaldehyde as a pale yellow oil (10.0 g, 45%). 1H NMR (CDCl3) δ 10.33 (s, 1H), 8.49 (m, 1H), 8.32 (m, 1H), 7.40 (m, 1H). LC/MS: 126 (M+H)+.

1. additionAfter the addition
2. temperaturecooled again to −78° C
3. customa pale yellow precipitate formed
4. temperaturemaintaining temperature below −55° C
5. waitAfter ten minutes
6. customthe cooling bath was removed
7. temperaturethe mixture slowly warmed to room temperature
8. customThe reaction was quenched with NH4Cl/H2O
9. additionNaHCO3/H2O was then added
10. extractionextracted three times with Et2O
11. washThe combined extracts were washed with brine
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated to a yellow oil
15. customThe residue was purified by chromatography on silica gel
16. washeluting with 25% EtOAc/hexane