反応 #7801

反応方程式

n-Butyllithium

4-bromo-2-fluoro benzyl cyanide

5-chlorobenzoxazole

n-Butyllithium

→

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

溶媒

—

hexanes

THF

THF

THF

反応条件

後処理

1. 1
   温度The reaction was then warmed at 0° C. for 1 h
2. 2
   その他prepared
3. 3
   workup.STIRRINGThe reaction was then stirred
4. 4
   温度at reflux overnight
5. 5
   その他quenched with sat. NaHCO3 (50 mL)
6. 6
   workup.ADDITIONAfter diluting the mixture with EtOAc (300 mL)
7. 7
   抽出the organic extract
8. 8
   洗浄was washed with H2O (50 mL)
9. 9
   乾燥dried (MgSO4)
10. 10
    ろ過filtered
11. 11
    濃縮concentrated in vacuo
12. 12
    その他The residue was purified by flash chromatography (silica gel, hexanes:EtOAc 5:1)

実験手順

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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