Dimethylformamide → 4-{[6-(2,4-Difluorophenyl)pyridin-2-yl]methyl}-3,5-difluorobenzonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(4-bromo-2,6-difluorobenzyl)-6-(2,4-difluorophenyl)pyridine (from Step D above, 7.32 g, 18.5 mmol) in wet DMF (200 mL of DMF and 2 mL water) was added Zn(CN)2 (1.74 g, 14.8 mmol), tris(dibenzylideneacetone)dipalladium (842 mg, 0.92 mmol), and 1,1′-bis(diphenylphosphino)ferrocene (1.23 g, 2.22 mmol) and heated to 120° C. for 1 hr (monitored via LCMS). After the reaction cooled to ambient temperature, the mixture was diluted with H2O and extracted with EtOAc (3×). The combined organic layers were washed with water (4×), brine (3×), dried over MgSO4, and condensed in vacuo. The crude material was purified via silica gel chromatography (hexanes/ethyl acetate) to give the title compound (6.1 g).

Provenance & Evidence