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

Temperature

50 °C

A mixture of 3-bromo-2,4-difluorophenylamine (0.6451 g, 3.10 mmol) and 3-fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile (0.915 g, 3.70 mmol) and potassium fluoride (0.5953 g, 10.2 mmol) in tetrahydrofuran (8 ml) was degassed with nitrogen for 15 min before adding tris(dibenzylideneacetone)dipalladium(0) (56.9 mg, 0.0621 mmol) and tri-tert-butylphosphine (1.24 ml of a 0.1 M solution in 1,4-dioxane, 0.124 mmol). The mixture was degassed for a further 5 min, then heated at 50° C. for 18 h under nitrogen. After cooling to ambient temperature, the mixture was partitioned between water (50 ml) and ethyl acetate (40 ml). The organic layer was washed with saturated aqueous NaCl (20 ml), dried (Na2SO4) and evaporated in vacuo. The residue was purified by chromatography (silica gel, 30% EtOAc/isohexane) to afford 0.5180 g (67%) of the title compound as a yellow solid: 1H NMR (360 MHz, CDCl3) δ 3.70 (2H, br s), 6.84–6.92 (2H, m), 7.44 (1H, t, J 8.4), 7.53 (1H, td, J 8.2, 5.1), 7.61 (1H, d, J 7.3).

1. customwas degassed with nitrogen for 15 min
2. customThe mixture was degassed for a further 5 min
3. temperatureAfter cooling to ambient temperature
4. customthe mixture was partitioned between water (50 ml) and ethyl acetate (40 ml)
5. washThe organic layer was washed with saturated aqueous NaCl (20 ml)
6. dry with materialdried (Na2SO4)
7. customevaporated in vacuo
8. customThe residue was purified by chromatography (silica gel, 30% EtOAc/isohexane)

ORD record

ord-62b286b07a1e42ff9ec66e49ce11ac08

Source dataset

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07005431B2