Picolinic acid → Diethyl 2-(5-methylpyridin-2-yl)malonate

Participants

Reaction Steps

To a stirred solution of 2-Iodo-5-methyl-pyridine (Preparation 272, 1 g, 4.57 mmol) and diethyl malonate (2.08 mL, 13.70 mmol) in anhydrous dioxane (12 mL) was added cesium carbonate (4.46 gm, 13.7 mmol) and the solution was degassed with argon for min. CuI (174 mg, 0.91 mmol) and picolinic acid (225 mg, 1.83 mmol) were added and the resultant mixture was heated in a sealed tube at 100° C. for 16 hours. The reaction mixture was cooled to room temperature, quenched with water (25 mL) and extracted with EtOAc (3×25 ml). The combined organic layers were washed with water (2×10 mL) and brine (10 mL), dried (Na2SO4) and evaporated in vacuo. The crude material was purified by column chromatography on silica gel (gradient of hexane:EtOAc 100:0 to 90:10) to afford the title compound as an oil in 23% yield, 300 mg.

Provenance & Evidence