Diethyl Malonate → HCID 54457771, compound

Participants

Reaction Steps

Diethyl malonate (229 mg, 1.43 nimol) was added dropwise via syringe over 5 min to a suspension of sodium hydride (52 mg of 60% oil dispension, 1.30 mmol) in 2.0 mL of N,N-dimethylformamide, and the mixture was stirred at room temperature until it became clear. A solution of 200 mg (0.65 mmol) of 6-(2-methanesulfonyloxyethyl)-4-methyl-2-(2,5-dimethylpyrrol-1-yl)pyridine (from Example 59, Step A) in 1.0 mL of N,N-dimethylformamide was added to the reaction followed by 72 mg (0.19 mmol) of tetrabutylammonium iodide, and the reaction was stirred at room temperature for 3 h followed by 15 h at 65° C. The reaction was diluted with ethyl acetate (30 mL) and washed with 15 mL of saturated aqueous sodium bicarbonate and 15 mL of saturated aqueous sodium chloride. The combined aqueous layers were extracted with 30 ml of ethyl acetate and the combined organic layers were dried (sodium sulfate), decanted and concentrated. The residue was purified by flash column chromatography on 50 g of silica gel, eluting with 500 mL of 5% ethyl acetate/hexane and 700 mL of of 10% ethyl acetate/hexane to give 97 mg (40% yield) of diethyl (2-(4-methyl-6-(2,5-dimethylpyrrol-1-yl)-2-pyridinyl)ethyl)malonate as a yellow oil.

Provenance & Evidence