Réaction #7795

Équation de réaction

n-Butyllithium

4-bromo-2-fluoro benzyl cyanide

benzoxazole

n-Butyllithium

→

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

Solvants

—

hexanes

THF

THF

THF

Conditions de réaction

Traitement

1. 1
   TempératureThe reaction was then warmed to 0° C. for 1 h
2. 2
   Autreprepared
3. 3
   workup.STIRRINGThe reaction mixture was then stirred
4. 4
   Températureat reflux overnight
5. 5
   Autrequenched with sat. NaHCO3 (50 mL)
6. 6
   workup.ADDITIONdiluted with EtOAc (300 mL)
7. 7
   LavageThe resulting organic layer was washed with H2O (1×50 mL)
8. 8
   Séchagedried (MgSO4)
9. 9
   Concentrationconcentrated in vacuo
10. 10
    AutreThe residue purified by flash chromatography (silica gel, hexanes:EtOAc 5:1)

Mode opératoire

To a stirred solution of benzoxazole (153 mg, 1.3 mmol) in 5 mL THF at −78° C., was added n-Butyllithium (640 μL, 2.5M in hexanes, 1.6 mmol). The reaction mixture was stirred for 15 min at −78° C. and ZnCl2 (3.9 mL, 1.0M solution in Et2O, 3.9 mmol) was added via a syringe. The reaction was then warmed to 0° C. for 1 h and a solution of 4-bromo-2-fluoro benzyl cyanide (214 mg, 1.0 mmol) in THF (2 mL) was added, along with Pd (a fine suspension prepared as follows: 200 μL n-Butyllithium, 2.5M in hexanes added to 144 mg PdCl2(PPh3)2 in 5 mL of THF). The reaction mixture was then stirred at reflux overnight, quenched with sat. NaHCO3 (50 mL) and diluted with EtOAc (300 mL). The resulting organic layer was washed with H2O (1×50 mL), dried (MgSO4) and concentrated in vacuo. The residue purified by flash chromatography (silica gel, hexanes:EtOAc 5:1) to afford the desired [4-(1,3-benzoxazol-2-yl)-2-fluorophenyl]acetonitrile as a yellow solid. 1H NMR (CD3OD, 300 MHz) δ 8.14 (q, 1H), 8.2 (q, 1H), 7.82 (m, 1H), 7.63 (m, 2H), 7.42 (m, 2H), 3.85 (s, 2H). MS (ESI) 253 (M+H)+.

Source