Qun‐Zheng Zhang, Zhi-Yuan Li, Le Zhang
Dec 1, 2020
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Journal
Russian Journal of Organic Chemistry
Abstract
There remain challenges for effectively synthesizing heterocycles containing both piperidine and pyridine rings, mainly due to the inefficient synthetic process mostly requiring long reaction times. This paper reports a simple and efficient method for the synthesis of [(3S,5R)-3-hydroxy-5-methylpiperidin-1-yl](2-methylpyridin-3-yl)methanone through six steps starting from D-pyroglutaminol. The key step involved the introduction of a chiral methyl group by alkylation of lithiated (3S,7aR)-3-phenyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one with methyl iodide, followed by reduction and rearrangement to generate a benzyl-protected piperidine intermediate. After deprotection and amide formation, the final product was obtained with an overall yield of 32% in a total time of ~80 h). With readily available and inexpensive starting material through an operationally simple process, the method holds potential for applications in organic synthesis of other piperidine- and pyridine-containing heterocycles.