2-Bromo-5-fluorobenzonitrile → 5'-Acetyl-4,2'-difluorobiphenyl-2-carbonitrile

Temperature

70 °C

To a degassed solution of 1-[4-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]ethanone (12 g, 45.43 mmol), 2-bromo-5-fluorobenzonitrile (9.09 g, 5.28 ml, 45.44 mmol), potassium fluoride (7.92 g, 136.31 mmol) and tris(dibenzylideneacetone)palladium(0) (0.834 g, 0.908 mmol) in THF (200 ml) and water (10 ml) was added tri-tert butylphosphine (10% weight solution) (0.368 g, 3.63 ml, 1.817 mmol). The reaction was heated at 70° C. for 14 h then allowed to cool to ambient temperature. The reaction was partitioned between water (200 ml) and ether (300 ml). The aqueous phase was extracted with ether (150 ml) and the combined organics washed with brine (200 ml), dried (MgSO4), filtered and evaporated to give a brown solid. The solid was dissolved in DCM and adsorbed onto silica. The crude product was chromatographed on silica (5-20% EtOAc in isohexane) to give the title product as a white solid (6.8 g): δH (400 MHz, CDCl3) 2.63 (3H, s), 7.31 (1H, t, J 9.0 Hz), 7.40-7.44 (1H, m), 7.50-7.53 (2H, m), 8.02-8.10 (2H, m).

1. temperatureto cool to ambient temperature
2. customThe reaction was partitioned between water (200 ml) and ether (300 ml)
3. extractionThe aqueous phase was extracted with ether (150 ml)
4. washthe combined organics washed with brine (200 ml)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. customevaporated
8. customto give a brown solid
9. customThe crude product was chromatographed on silica (5-20% EtOAc in isohexane)

ORD record

ord-13bb162f9eca4037acf08c41805da85d

Source dataset

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06969716B2