Synthesis of 5-(p-Toluoyl)-1-Methylpyrrole-2-Acetic Acid [Tolmetin]

5-(p-톨루오일)-1-메틸피롤-2-아세트산의 합성

A facile method for tolmetin, which is a potent antiinflammatory agent, is described. Friedel-Crafts reaction of 1-methylpyrrole with ethyl ${\alpha}-chloro-{\alpha}-(methylthio)acetate$ (1) gave ethyl ${\alpha}-methylthio$-1-methyl-2-pyrroleacetate (4), which was readily converted into ethyl 1-methyl-2-pyrroleacetate (5) by reductive desulfurization with zinc dust in acetic acid. Tolmetin was synthesized by Friedel-Crafts acylation of (5) with p-toluoyl chloride, followed by hydrolysis of the resultant ethyl 5-(p-toluoyl)-1-methylpyrrole-2-acetate (6).