2-Bromobenzonitrile → 2-(2-Fluorophenyl)benzonitrile

A mixture of 2-bromobenzonitrile (5.1 g, 28 mmol), 2-fluorobenzeneboronic acid (4.9 g, 35 mmol) and potassium fluoride (5.37 g, 92 mmol) in THF (50 ml) was degassed with nitrogen for 10 min. This mixture was then treated with tris(dibenzylideneacetone)dipalladium(0) (510 mg, 0.56 mmol) followed by tri-tert-butylphosphine (5.6 ml of a 0.2 M solution in 1,4-dioxane, 1.12 mmol) and the reaction was stirred at ambient temperature for 15 min. The resulting slurry was then heated at 50° C. for 30 min in order to consume remaining starting materials and then cooled to ambient temperature. The reaction mixture was filtered, washing the filter-cake with tetrahydrofuran (50 ml). The filtrate was evaporated to dryness and the residue partitioned between ethyl acetate and water. The organics were washed with brine, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography (silica gel, 5-10% EtOAc/isohexane) gave 5.5 g (100%) of the title compound as a pale yellow solid: 1H NMR (360 MHz, CDCl3) δ 7.19-7.29 (2H, m), 7.40-7.52 (4H, m), 7.65 (1H, ddd, J 8, 8, 1 Hz), 7.79 (1H, dd, J 8, 1 Hz).

1. customwas degassed with nitrogen for 10 min
2. temperatureThe resulting slurry was then heated at 50° C. for 30 min in order
3. customto consume
4. temperaturecooled to ambient temperature
5. filtrationThe reaction mixture was filtered
6. washwashing the
7. filtrationfilter-cake with tetrahydrofuran (50 ml)
8. customThe filtrate was evaporated to dryness
9. customthe residue partitioned between ethyl acetate and water
10. washThe organics were washed with brine
11. dry with materialdried over anhydrous magnesium sulfate
12. filtrationfiltered and pre-adsorbed onto silica
13. customPurification by chromatography (silica gel, 5-10% EtOAc/isohexane)

ORD record

ord-b67197151a3c4f998722522252b2bc26

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06936608B2