5-Methylbenzoxazole → [2-Fluoro-4-(5-methyl-1,3-benzoxazol-2-yl)phenyl]acetonitrile

Temperature

-78 °C

To a stirred solution of 5-methylbenzoxazole (173 mg, 1.3 mmol) in THP (5 mL) 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. followed by the addition of ZnCl2 (3.9 mL, 1M in Et2O, 3.9 mmol) via a syringe. The reaction mixture was warmed at 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 Pd0 (a fresh 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 mixture was refluxed overnight and quenched with sat. NaHCO3 (50 mL). After extraction with EtOAc (3×75 mL), the organic layers were combined, washed with brine (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) to afford the desired [2-fluoro-4-(5-methyl-1,3-benzoxazol-2-yl)phenyl]acetonitrile as yellow solid. 1H NMR (CD3OD, 300 MHz), δ 8.07 (d, 1H), 7.95 (d, 1H), 7.64 (m, 2H), 7.40 (s, 1H), 7.20 (d, 1H), 3.90 (s, 1H). MS (ESI) 267 (M+H)+.

1. temperatureThe reaction mixture was warmed at 0° C. for 1 h
2. customprepared
3. temperatureThe mixture was refluxed overnight
4. customquenched with sat. NaHCO3 (50 mL)
5. extractionAfter extraction with EtOAc (3×75 mL)
6. washwashed with brine (50 mL)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo
9. customThe residue was purified by chromatography on silica gel using
10. additiona mixture of hexanes:EtOAc (5:1)

ORD record

ord-d1f66853356d467193b9ad4264bc615e

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07087601B2