Sodium Hydroxide → 5'-Acetyl-2'-fluorobiphenyl-2-carbonitrile

1-(3-Chloro-4-fluorophenyl)ethanone (0.86 g, 5.0 mmol), 2-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)benzonitrile (1.37 g, 6.0 mmol) (prepared according to the procedure described in WO 02/74773) and potassium fluoride (0.96 g, 16.5 mmol) were suspended in tetrahydrofuran (20 ml) and the mixture degassed with nitrogen for 30 min. Tris(dibenzylidineacetone)dipalladium(0) (0.14 g, 0.15 mmol) and tri-tert-butylphosphine (0.3M in 1,4-dioxane, 1.0 ml) were added and the mixture stirred at room temperature for 1 h then heated at 50° C. for 18 h. The mixture was allowed to cool to room temperature and then poured into 0.5N sodium hydroxide solution (300 ml) and stirred for 30 min. The solid was filtered, washed with water (50 ml) and isohexane (50 ml) and the brown solid left to air-dry. The solid was purified by flash column chromatography on silica eluting with isohexane on a gradient of ethyl acetate (10-30%). Collecting the appropriate fractions gave 5′-acetyl-2′-fluorobiphenyl-2-carbonitrile (0.31 g, 26%) as a yellow solid: δH(400 MHz, CDCl3) 2.64 (3H, s), 7.31 (1H, t, J 8.8 Hz), 7.52-7.56 (2H, m), 7.68-7.72 (1H, m), 7.81 (1H, dd, J 0.8, 7.4 Hz), 8.04-8.09 (2H, m).

1. customthe mixture degassed with nitrogen for 30 min
2. temperaturethen heated at 50° C. for 18 h
3. temperatureto cool to room temperature
4. stirringstirred for 30 min
5. filtrationThe solid was filtered
6. washwashed with water (50 ml) and isohexane (50 ml)
7. waitthe brown solid left
8. customto air-dry
9. customThe solid was purified by flash column chromatography on silica eluting with isohexane on a gradient of ethyl acetate (10-30%)
10. customCollecting the appropriate fractions

ORD record

ord-ec36dbef8a2a4d239cc99bdc9c08b137

Source dataset

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06969716B2