Tris(1,1-dimethylethyl)phosphine → 3'-Amino-4,2',6'-trifluorobiphenyl-2-carbonitrile

Temperature

50 °C

A solution of 3-bromo-2,4-difluorophenylamine (from Example 2, step b) (5.2 g, 25 mmol) and 5-fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile (7.10 g, 28.8 mmol) in tetrahydrofuran (95 ml) and water (5 ml) was treated with potassium fluoride (4.8 g, 82.5 mmol) and this mixture was degassed with nitrogen for 10 min before adding tris(dibenzylideneacetone)dipalladium(0) (460 mg, 0.5 mmol) and tri-tert-butylphosphine (2.5 ml of a 0.2 M solution in 1,4-dioxane, 0.5 mmol). The reaction was then heated at 50° C. for 2 h then cooled to ambient temperature. The mixture was poured into ice-cold 0.5 N sodium hydroxide (750 ml), stirred for 10 min and the solid collected by filtration. This was triturated with water and dried to afford 3′-amino-4,2′,6′-trifluorobiphenyl-2-carbonitrile as a grey powder (6.6 g), which was used without further purification: 1H NMR (360 MHz, CDCl3) δ 3.74 (2H, br s), 6.79–6.89 (2H, m), 7.36–7.42 (1H, m), 7.45–7.51 (2H, m).

1. customthis mixture was degassed with nitrogen for 10 min
2. temperaturethen cooled to ambient temperature
3. filtrationthe solid collected by filtration
4. customThis was triturated with water
5. customdried

ORD record

ord-ccdd763186ed48778098b1d8695a0f8d

Source dataset

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07005431B2