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5-(p-톨루오일)-메틸피롤-2-아세트산의 합성

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

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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).

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