반응 #162386

반응 방정식

N,N-Dimethylformamide

n-butyllithium

N,N-diisopropylamine

2-Fluoropyridine

→

2-fluoronicotinaldehyde

수율 45.9%

용매

THF

반응 조건

후처리

1. 1
   workup.ADDITIONAfter the addition
2. 2
   온도cooled again to −78° C
3. 3
   기타a pale yellow precipitate formed
4. 4
   온도maintaining temperature below −55° C
5. 5
   workup.WAITAfter ten minutes
6. 6
   기타the cooling bath was removed
7. 7
   온도the mixture slowly warmed to room temperature
8. 8
   기타The reaction was quenched with NH4Cl/H2O
9. 9
   workup.ADDITIONNaHCO3/H2O was then added
10. 10
    추출extracted three times with Et2O
11. 11
    세척The combined extracts were washed with brine
12. 12
    건조dried over MgSO4
13. 13
    여과filtered
14. 14
    농축concentrated to a yellow oil
15. 15
    기타The residue was purified by chromatography on silica gel
16. 16
    세척eluting with 25% EtOAc/hexane

실험 절차

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)+.

출처