تفاعل #7801

معادلة التفاعل

n-Butyllithium

4-bromo-2-fluoro benzyl cyanide

5-chlorobenzoxazole

n-Butyllithium

→

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

المذيبات

—

hexanes

THF

THF

THF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction was then warmed at 0° C. for 1 h
2. 2
   أخرىprepared
3. 3
   workup.STIRRINGThe reaction was then stirred
4. 4
   درجة الحرارةat reflux overnight
5. 5
   أخرىquenched with sat. NaHCO3 (50 mL)
6. 6
   workup.ADDITIONAfter diluting the mixture with EtOAc (300 mL)
7. 7
   استخلاصthe organic extract
8. 8
   غسيلwas washed with H2O (50 mL)
9. 9
   تجفيفdried (MgSO4)
10. 10
    ترشيحfiltered
11. 11
    تركيزconcentrated in vacuo
12. 12
    أخرىThe residue was purified by flash chromatography (silica gel, hexanes:EtOAc 5:1)

الإجراء التجريبي

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)+.

المصدر