Hydrochloric Acid → Diethyl 2-(3-(trifluoromethyl)pyridin-2-yl)malonate

関与物質

反応手順

8.73 g of sodium hydride (55% oil dispersion) was suspended in 100 ml of 1,4-dioxane. Into this, 32.03 g of diethyl malonate was added dropwise over a period of about 1 hour at 60° C. under a nitrogen atmosphere. The mixture was stirred further for 0.5 hours at the same temperature, then, 8.26 g of copper chloride (I) was added to the mixture. Thereafter, into the mixture, a solution prepared by dissolving 15.00 g of 2-chloro-3-(trifluoromethyl)pyridine in 50 ml of 1,4-dioxane at 80° C. was dropped. The mixture was stirred for 16 hours under reflux with heating. The reaction mixture was allowed to cool to room temperature, and to the reaction mixture was added 15 ml of concentrated hydrochloric acid. To the mixture were added water and ethyl acetate, and the mixture was filtrated through celite. The filtrate was liquid-separated. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. 51.14 g of the resultant residue was subjected to silica gel column chromatography, to obtain 6.90 g of diethyl (3-trifluoromethyl-2-pyridyl)malonate.

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