Concise Large-Scale Synthesis of the Highly Active Cephalosporin Cefdaloxime

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• 作者：Bernhard Kammermeier ; Gerhard Beck ; Josef Reitz ; Christian Sommer ; Theo Wollmann ; and Heiner Jendralla
• 刊名：Organic Process Research & Development
• 出版年：1997
• 出版时间：March 1997
• 年：1997
• 卷：1
• 期：2
• 页码：121 - 123
• 全文大小：143K
• 年卷期：v.1,no.2(March 1997)
• ISSN：1520-586X

文摘

Cefdaloxime (1a) is the bioactive principle of the1-(S)-(pivaloyloxy)ethyl ester prodrug HR916K (1b). Toprovidematerial for biological investigations a short and efficientlarge-scale synthesis of 1a was developed, which avoidschromatographic purification steps. Commercially available(6R,7R)-7-amino-3-(methoxymethyl)-3-cephem-4-carboxylic acid (AMCA)(2) is acylated with trityl-protectedmercaptobenzothiazolethioester in the presence of bis(trimethylsilyl)acetamide toyieldtritylated cefdaloxime. The trityl group is then removedbytreatment with formic acid, followed by pH-adjustedprecipitation of 1a. For a final purification, which has toconsidercefdaloxime specific side reactions, crude 1a is dissolvedindimethyl sulfoxide and precipitated with methanol toobtain1a in 66% overall yield on a kilogram scale.