A simple and efficient synthesis of N-[3-chloro-4-(4-chlorophenoxy)-phenyl]-2-hydroxy-3,5-diiodobenzamide, rafoxanide

N-[3-氯-4-(4-氯苯氧基)苯基]-2-羟基-3,5-二碘苯甲酰胺(拉福沙尼)的简便高效合成

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Abstract

A method for the synthesis of rafoxanide 6, a halogenated salicylanilide used as an efficient anthelmintic in sheep and cattle, is presented. Rafoxanide 6 was synthesized in only three steps from readily available 4-chlorophenol with 74% overall yield. The synthesis has two key stages: the first was salicylic acid iodination, adding iodine in the presence of hydrogen peroxide, which allowed obtaining a 95% yield. The second key stage was the reaction of 3,5-diiodosalicylic acid 5 with aminoether 4, where salicylic acid chloride was formed in situ with PCl(3) achieving 82% yield. Chemical characterization of both intermediates and final product was achieved through physical and spectroscopic (IR, NMR and MS) techniques. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11696-023-02846-9.

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