Ethyl 3-(trimethylsilyl)propynoate → 4-[1-[6-(2,4-Difluorophenyl)pyridin-2-yl]-2-oxo-4-(trimethylsilyl)but-3-yn-1-yl]-3,5-difluorobenzonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-{[6-(2,4-difluorophenyl)pyridin-2-yl]methyl}-3,5-difluorobenzonitrile (from Step E above, 6.10 g, 17.83 mmol) in THF (200 mL) was added lithium bis(trimethylsilyl)amide (53.49 mL, 1.0 M in THF) at −78° C. After stirring 1¼ h at −78° C., ethyl 3-(trimethylsilyl)prop-2-ynoate (4.01 mL, 21.37 mmol) was added to the reaction mixture. The reaction continued to stir at −78° C. for 1 hr and was warmed to −20° C. until the reaction was complete via LMCS. The reaction was quenched with aqueous NH4Cl and extracted with EtOAc (3×). The combined organic layers were washed with 1N HCl (1×), water, brine, dried over MgSO4, and condensed. The crude material was purified via silica gel chromatography (hexanes/methylene chloride) to give the title compound (7.0 g).

Provenance & Evidence