Sodium hydride → 4-ethynyl-2-fluorobenzonitrile

To a solution of 2-fluoro-4-(3-hydroxy-3-methyl-but-1-ynyl)-benzonitrile (2.6 g, 13 mmol) in toluene (55 mL) was added NaH (53 mg of a 60% suspension in mineral oil, 1.3 mmol). The reaction mixture was heated to reflux. After refluxing for several hours, heating was discontinued, and the cooled reaction mixture was quenched by the addition of 2M Na2CO3 solution. The layers were separated and the toluene layer was washed with H2O (2×20 mL), brine (25 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude product. The crude material was purified by flash chromatography eluting with a gradient from 0% to 10% ethyl acetate/hexane to afford 4-ethynyl-2-fluoro-benzonitrile (1.25 g, 66% yield). 1H-NMR (400 MHz, CDCl3): δ 7.61-7.57 (1H, m), 7.38-7.30 (2H, m), 3.36 (1H, s).

1. temperatureThe reaction mixture was heated to reflux
2. temperatureAfter refluxing for several hours
3. temperatureheating
4. customthe cooled reaction mixture
5. customwas quenched by the addition of 2M Na2CO3 solution
6. customThe layers were separated
7. washthe toluene layer was washed with H2O (2×20 mL), brine (25 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto afford the crude product
12. customThe crude material was purified by flash chromatography
13. washeluting with a gradient from 0% to 10% ethyl acetate/hexane

ORD record

ord-fa145819ab29475ea97f144a8f865c21

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08013001B2