Sodium hydride → tert-Butyl Methyl [3-Cyano-5-(trifluoromethyl)pyridin-2-yl]malonate

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To a suspension of sodium hydride (0.752 g, 29.8 mmol) in THF (18 mL) under nitrogen was added dropwise a solution of tert-butyl methyl malonate (3.18 mL, 17.9 mmol) in dry THF (15 mL) via syringe during a period of 15 min. The reaction mixture was stirred for 30 min before a solution of 2-chloro-5-(trifluoromethyl)nicotinonitrile (4.0 g, 14.5 mmol) in THF (30 mL) was added slowly. After being stirred at room temperature overnight, the reaction mixture was quenched with aqueous NH4Cl. THF was removed in vacuo and the aqueous solution was extracted with EtOAc three times. The combined organic layers were dried over MgSO4, filtered, and evaporated in vacuo. The crude brown product (7.1 g) was purified by flash chromatography (10:90 EtOAc/hexanes) to afford 4.20 g (84%) of desired product as a yellow oil. LC-MS calculated for C15H15F3N2O4: (M+H)+345; found 245.0 (M−CO2tBu+H+1)+.

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