Practical synthesis of fenbufen ethanolamide

The ongoing interest in ethanolamide derivatives of anti-inflammatory drugs as potential synthetic cannabinoids and mechanistic tools for the study of cannabinoid and vanilloid receptors prompted us to develop a practical gram scale synthesis for the hitherto unknown ethanolamide of fenbufen. Dehydration of fenbufen leads to intramolecular ring closure yielding bright pink crystals of the intramolecular enol ester. Reaction of this activated but stable intermediate with ethanolamine leads to the title compound in good yield and purity without the necessity to remove coupling reagents or residual activating groups, such as N, N-dialkyl ureas and fluorinated phenols.