反応 #162386

反応方程式

N,N-Dimethylformamide

n-butyllithium

N,N-diisopropylamine

2-Fluoropyridine

→

2-fluoronicotinaldehyde

収率 45.9%

溶媒

THF

反応条件

後処理

1. 1
   workup.ADDITIONAfter the addition
2. 2
   温度cooled again to −78° C
3. 3
   その他a pale yellow precipitate formed
4. 4
   温度maintaining temperature below −55° C
5. 5
   workup.WAITAfter ten minutes
6. 6
   その他the cooling bath was removed
7. 7
   温度the mixture slowly warmed to room temperature
8. 8
   その他The reaction was quenched with NH4Cl/H2O
9. 9
   workup.ADDITIONNaHCO3/H2O was then added
10. 10
    抽出extracted three times with Et2O
11. 11
    洗浄The combined extracts were washed with brine
12. 12
    乾燥dried over MgSO4
13. 13
    ろ過filtered
14. 14
    濃縮concentrated to a yellow oil
15. 15
    その他The residue was purified by chromatography on silica gel
16. 16
    洗浄eluting with 25% EtOAc/hexane

実験手順

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)+.

出典