Sodium Bicarbonate → [2-Fluoro-4-(6-methyl-1,3-benzoxazol-2-yl)phenyl]acetonitrile

Temperature

-78 °C

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)+.

1. customThe resulting reaction mixture
2. temperatureAfter warming up the reaction mixture at 0° C. for 1 h
3. customprepared
4. temperatureThe mixture was then heated
5. temperatureunder reflux overnight
6. extractionextracted with EtOAc (3×150 mL)
7. washwashed with H2O (50 mL)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo
10. customThe residue was purified by chromatography on silica gel using
11. additiona mixture of hexanes:EtOAc (5:1) as eluant

ORD record

ord-a318cc3736b248789a9b6636f289d356

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07087601B2