Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

The <i>N</i>,<i>O</i>-acetal derived from diethyl mesoxalate (DEMO) undergoes elimination of acetic acid upon treatment with a base, leading to the formation of <i>N</i>-acylimine in situ. Lithium acetylide readily attacks the imino group to afford <i>N</i>,1,1-tricarbonylated propargylamines. When the resulting propargylamine reacts with butyllithium, ring closure occurs between the ethynyl and carbamoyl groups, yielding 2,5-disubstituted oxazole-4-carboxylates. This cyclization also occurs when the propargylamine is heated with ammonium acetate, resulting in double activation.