2,4-Difluoroaniline → HCID 67491765, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-chloro-2-methylnicotinonitrile (2.01 g, 13 mmol), 2,4-difluorobenzenamine (2.0 mL, 20 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.36 g, 0.40 mmol), 2-dicyclohexylphosphino-2′-(n,n-dimethylamino)biphenyl (0.31 g, 0.79 mmol, Dave-Phos) in 8.0 mL of THF at RT was treated with bis(trimethylsilyl)amino)lithium (28 mL of 1.0 M in THF solution, 28 mmol) drop wise. The mixture was heated at 50° C. in an oil bath for 0.5 h, then cooled to RT, quenched with NH4Cl and diluted with EtOAc. The mixture was filtered through a pad of Celite to remove some Pd black. The filtrate was transferred to a separatory funnel. The EtOAc layer was washed with brine, dried and concentrated. Purification of the resulting brown residue on an ISCO column (120 g, with 25-75% EtOAc in Hexanes) afforded 6-(2,4-difluorophenylamino)-2-methylnicotinonitrile afforded the title compound as a tan crystalline solid. MS (ESI, pos.ion) m/z: M+1=246.0

Provenance & Evidence