Benzoxazole → 4-(Benzoxazol-2-yl)-2-fluorophenylacetonitrile

Temperature

-78 °C

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)+.

1. temperatureThe reaction was then warmed to 0° C. for 1 h
2. customprepared
3. stirringThe reaction mixture was then stirred
4. temperatureat reflux overnight
5. customquenched with sat. NaHCO3 (50 mL)
6. additiondiluted with EtOAc (300 mL)
7. washThe resulting organic layer was washed with H2O (1×50 mL)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo
10. customThe residue purified by flash chromatography (silica gel, hexanes:EtOAc 5:1)

ORD record

ord-042cc444894b477f82d1d626a97f37a9

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07087601B2