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

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-{[6-(2,4-difluorophenyl)pyridin-2-yl]methyl}-4-fluorobenzonitrile (from Step C above, 30.0 g, 92.3 mmol) in THF (700 mL) was added LiHMDS (276 mL, 276 mmol, 1M solution in THF) via cannula at −78° C. After stirring for 1 hr and 15 min at −78° C., ethyl 3-(trimethylsilyl)prop-2-ynoate (4.01 mL, 21.37 mmol) was added. The reaction was allowed to stir at −78° C. for 1 hr and was allowed to warm to 0° C. over 3 hours. The reaction was quenched with aqueous NH4Cl, extracted with ethyl acetate (2×). The organic layers were combined, washed with 0.5 N HCl, water, brine (2×), dried over MgSO4, and condensed in vacuo to yield a black oil. The crude material was purified via silica gel chromatography (100% CH2Cl2) to give the title compound (40.0 g).

Provenance & Evidence