Hydrochloric Acid → Methyl 2-[(5-cyanopyridin-3-yl)methyl]-3-oxobutanoate

Participants

Reaction Conditions

Reaction Steps

To a suspension of 84 mg (2.11 mmol) of sodium hydride (60% in oil) in 3 mL of anhydrous DME is added, under argon at 0° C., 0.23 ml (2.11 mmol) of methyl acetoacetate. The reaction medium is stirred for 30 minutes at 0° C. and for 30 minutes at room temperature, followed by addition of 161 mg (1.06 mmol) of 5-(chloromethyl)pyridine-3-carbonitrile diluted in 1 mL of DME and 29 mg (0.11 mmol) of tetrabutylammonium iodide. The medium is then heated at 65° C. for 4 hours. After cooling to room temperature, the medium is taken up in 10 mL or water, neutralized by adding 0.1N HCl, and then extracted with EtOAc (2×40 mL), dried over Na2SO4, concentrated under reduced pressure and purified by chromatography on a column of silica gel, eluting with a cyclohexane/EtOAc mixture (8/2). 140 mg of methyl 2-[(5-cyanopyridin-3-yl)methyl]-3-oxobutanoate are obtained in the form of a colourless oil.

Provenance & Evidence