Sodium hydride → (3-Chloro-2,5,6-trifluoro-pyridin-4-yl)-acetic acid benzyl ester

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3-Chloro-2,4,5,6-tetrafluoropyridine (33.1 g, 178 mmol) and dibenzyl malonate (44.5 ml, 178 mmol) were dissolved in anhydrous DMF (360 ml) under nitrogen atmosphere. The mixture (142) was then cooled in an ice bath. To a stirred mixture, was portionwise added 60% sodium hydride (15.68 g, 392 mmol) during 2.5 hr. The mixture was then stirred in a water bath for ca. 15 hr. The mixture was neutralized with aqueous saturated ammonium chloride solution and the mixture was partitioned between ether and water. Ether layer was taken, washed with water twice, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo to give a crude product as an yellow oil. The crude product was then dissolved in DMSO (200 ml) and stirred with water (3.2 ml) in an oil bath (130˜140° C.) for 3 hr. After cooling to room temperature, water was added to the mixture and the product was extracted with ether. The ether layer was washed with water twice, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo to give a light brown oil. The crude product was purified by silica gel column chromatography (eluent, ether:hexane (1:9)) to afford 41.9 g (74% for two steps) of (3-chloro-2,5,6-trifluoro-pyridin-4-yl)-acetic acid benzyl ester as a white solid. m.p. 87-92° C.; 1H NMR (200 MHz, CDCl3) δδ 3.96 (2H, d, J=1.6 Hz), 5.19 (2H, s), 7.30-7.39 (5H, m).

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