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Multi-Gram Scale Synthesis and Characterization of Mometasone Furoate EP Impurity C
Riccardo Ronchetti1, Luigi Alfonso Pannone1, Bruno Cerra1
1Laboratory of Medicinal and Advanced Synthetic Chemistry (Lab MASC), Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06122 Perugia, Italy.
Abstract:
Mometasone furoate is a synthetic corticosteroid used in the treatment of skin inflammatory conditions, hay fever and asthma. The industrial manufacturing routes to mometasone furoate are generally accompanied by the formation of numerous process impurities that need to be detected and quantified, as requested by regulatory authorities. The ready availability of such impurities in the required quantity and purity is therefore essential for toxicological studies, analytical method development and process validation. Herein, we report the multi-gram scale preparation of 21'-chloro-(16'α-methyl-3',11',20'-trioxo-pregna-1',4'-dien-17'-yl)-furan-2-carboxylate (mometasone furoate EP impurity C), one of the known impurities of mometasone furoate. This study also includes the systematic investigation of the final acylation step, as well as the characterization of the difuroate enol ether intermediate and its conversion to the target impurity C.
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