Synthesis of 2,3‐Disubstituted 4‐Pyridone From a β‐Aminocarboxylate Derivative and Acetoacetate

Abstract

The reaction of diethyl aminomethylenemalonate with ethyl acetoacetate proceeded, when catalyzed by anhydrous hydrogen chloride, toward a respectively substituted α‐ instead of γ‐pyridone derivative formation, contrary to the literature report. Additionally, it was found that the amine used as a starting component in this reaction showed a great tendency to autocondensation under the influence of anhydrous hydrogen chloride to yield 5‐ethoxycarbonyl‐2‐pyridone. The most convenient method to prepare 4‐pyridone 2,3‐disubstituted derivative appeared to be a three‐step synthesis, starting from a chain enamine formation, which was subjected to cyclization, followed by oxidation of the last intermediate. The usefulness of the stepwise synthesis was demonstrated on the 3‐ethoxycarbonyl‐2‐methyl‐4‐pyridone preparation as an example.

Keywords:

• Aminomethylenemalonate
• autocondensation
• γ‐pyridone
• α‐pyridone