5-Chlorobenzoxazole → [4-(5-Chloro-1,3-benzoxazol-2-yl)-2-fluorophenyl]acetonitrile

Temperature

-78 °C

To a stirred solution of 5-chlorobenzoxazole (200 mg, 1.3 mmol) in 5 mL THF at −78° C., was added n-Butyllithium (640 μL, 2.5M in hexane, 1.6 mmol). The reaction 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 was then warmed 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 reaction was then stirred at reflux overnight and quenched with sat. NaHCO3 (50 mL). After diluting the mixture with EtOAc (300 mL), the organic extract was washed with H2O (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, hexanes:EtOAc 5:1) to afford the desired [4-(5-chloro-1,3-benzoxazol-2-yl)-2-fluorophenyl]acetonitrile as yellow solid. 1H NMR (CD3OD, 300 Hz), δ8.10(d, 1H), 7.99 (d, 1H), 7.79 (d, 1H), 7.68 (t, 1H), 7.52 (d, 1H), 7.39 (q, 1H), 3.90 (s, 1H). MS (ESI) 287 (M+H)+.

1. temperatureThe reaction was then warmed at 0° C. for 1 h
2. customprepared
3. stirringThe reaction was then stirred
4. temperatureat reflux overnight
5. customquenched with sat. NaHCO3 (50 mL)
6. additionAfter diluting the mixture with EtOAc (300 mL)
7. extractionthe organic extract
8. washwas washed with H2O (50 mL)
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by flash chromatography (silica gel, hexanes:EtOAc 5:1)

ORD record

ord-c38c224bdbf645f49b58fc61a53b9b3d

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07087601B2