Reduction of Ethyl Benzoylacetate and Selective Protection of 2-(3-Hydroxy-1-phenylpropyl)-4-methylphenol: A New and Facile Synthesis of Tolterodine

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• 作者：Kathlia A. De Castro ; Jungnam Ko ; Daejong Park ; Sungdae Park ; Hakjune Rhee
• 刊名：Organic Process Research & Development
• 出版年：2007
• 出版时间：September 2007
• 年：2007
• 卷：11
• 期：5
• 页码：918 - 921
• 全文大小：86K
• 年卷期：v.11,no.5(September 2007)
• ISSN：1520-586X

文摘

A new and facile synthesis of tolterodine using ethyl benzoylacetate as the starting material was developed. Reduction using sodium borohydride in methanol followed by Friedel–Crafts alkylation utilizing FeCl₃·6H₂O as catalyst lead to the known 2-(3-hydroxy-1-phenylpropyl)-4-methylphenol intermediate. Consecutive protection of phenolic OH with p-toluenesulfonyl chloride via two-phase reaction and conversion of aliphatic OH using p-nitrobenzenesulfonyl chloride facilitates direct substitution of diisopropylamine. After simultaneous deprotection of the tosyl group, optically pure (R)-tolterodine·L-tartrate was obtained by resolution using L-tartaric acid with 99.99% purity.