Réaction #7797

Équation de réaction

6-methylbenzoxazole

n-Butyllithium

4-bromo-2-fluoro benzyl cyanide

n-Butyllithium

NaHCO3

→

[2-fluoro-4-(6-methyl-1,3-benzoxazol-2-yl)phenyl]acetonitrile

Solvants

THF

THF

—

hexanes

THF

Conditions de réaction

Traitement

1. 1
   AutreThe resulting reaction mixture
2. 2
   TempératureAfter warming up the reaction mixture at 0° C. for 1 h
3. 3
   Autreprepared
4. 4
   TempératureThe mixture was then heated
5. 5
   Températureunder reflux overnight
6. 6
   Extractionextracted with EtOAc (3×150 mL)
7. 7
   Lavagewashed with H2O (50 mL)
8. 8
   Séchagedried (MgSO4)
9. 9
   Concentrationconcentrated in vacuo
10. 10
    AutreThe residue was purified by chromatography on silica gel using
11. 11
    workup.ADDITIONa mixture of hexanes:EtOAc (5:1) as eluant

Mode opératoire

To a stirred solution of 6-methylbenzoxazole (173 mg, 1.3 mmol) in THF (5 mL) at −78° C., was added n-Butyllithium (640 μL, 2.5M in hexanes, 1.6 mmol). The resulting reaction mixture was stirred for 15 min at −78° C. and ZnCl2 (3.9 mL, 1M in Et2O, 3.9 mmol) was added via a syringe. After warming up the reaction mixture 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 mixture was then heated under reflux overnight. The mixture was hydrolized with sat. NaHCO3 (50 mL) and extracted with EtOAc (3×150 mL). The organic layers were combined, washed with H2O (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by chromatography on silica gel using a mixture of hexanes:EtOAc (5:1) as eluant to afford [2-fluoro-4-(6-methyl-1,3-benzoxazol-2-yl)phenyl]acetonitrile as yellow solid. 1H NMR (CD3OD, 300 MHz), δ8.07 (d, 1H), 7.95(d, 1H), 7.64(m, 2H), 7.40(s, 1H), 7.20(d, 11H), 3.90(s, 1H). MS (ESI) 267 (M+H)+.

Source