반응 #7801

반응 방정식

n-Butyllithium

4-bromo-2-fluoro benzyl cyanide

5-chlorobenzoxazole

n-Butyllithium

→

[4-(5-chloro-1,3-benzoxazol-2-yl)-2-fluorophenyl]acetonitrile

용매

—

hexanes

THF

THF

THF

반응 조건

후처리

1. 1
   온도The reaction was then warmed at 0° C. for 1 h
2. 2
   기타prepared
3. 3
   workup.STIRRINGThe reaction was then stirred
4. 4
   온도at reflux overnight
5. 5
   기타quenched with sat. NaHCO3 (50 mL)
6. 6
   workup.ADDITIONAfter diluting the mixture with EtOAc (300 mL)
7. 7
   추출the organic extract
8. 8
   세척was washed with H2O (50 mL)
9. 9
   건조dried (MgSO4)
10. 10
    여과filtered
11. 11
    농축concentrated in vacuo
12. 12
    기타The residue was purified by flash chromatography (silica gel, hexanes:EtOAc 5:1)

실험 절차

To a stirred solution of 5-chlorobenzoxazole (200 mg, 1.3 mmol) in 5 mL THF at −78° C., was added n-Butyllithium (640 μL, 2.5M in hexane, 1.6 mmol). The reaction was stirred for 15 min at −78° C. followed by the addition of ZnCl2 (3.9 mL, 1M in Et2O, 3.9 mmol) via a syringe. The reaction was then warmed at 0° C. for 1 h. A solution of 4-bromo-2-fluoro benzyl cyanide (214 mg, 1.0 mmol) in THF (2 mL) was added, along with Pd0 (a fresh suspension prepared as follows: 200 μL, n-Butyllithium, 2.5M in hexanes added to 144 mg of PdCl2(PPh3)2 in 5 mL of THF). The reaction was then stirred at reflux overnight and quenched with sat. NaHCO3 (50 mL). After diluting the mixture with EtOAc (300 mL), the organic extract was washed with H2O (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, hexanes:EtOAc 5:1) to afford the desired [4-(5-chloro-1,3-benzoxazol-2-yl)-2-fluorophenyl]acetonitrile as yellow solid. 1H NMR (CD3OD, 300 Hz), δ8.10(d, 1H), 7.99 (d, 1H), 7.79 (d, 1H), 7.68 (t, 1H), 7.52 (d, 1H), 7.39 (q, 1H), 3.90 (s, 1H). MS (ESI) 287 (M+H)+.

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