Non-steroidal antiinflammatory agents. 1. A novel synthesis of 1-methyl-5-p-tolylpyrrole-2-acetic acid (tolmetin)

Article abstract of DOI:10.1002/jhet.5570190647

A four-step preparation of 1-methyl-5-p-tolylpyrrole-2-acetic acid (Tolmetin) is reported starting from 1-methyl-2-p-tolylpyrrole. Formylation of this compound followed by condensation with methyl(methylthio)methyl sulfoxide furnished 1-(methylsulfinyl)-1-methylthio-2-(1-methyl-5-p-tolyl-2-pyrrolyl)ethylene. Pummerer rearrangement of the latter compound gave ethyl 1-methyl-5-p-tolypyrrole-2-acetate, which was hydrolyzed in alkaline medium to afford Tolmetin.