Synthesis of [(3S,5R)-3-Hydroxy-5-methylpiperidin-1-yl](2-methylpyridin-3-yl)methanone

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 [(3 S ,5 R )-3-hydroxy-5-methyl...

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Bibliographic Details
Published in:Russian journal of organic chemistry 2020-12, Vol.56 (12), p.2201-2206
Main Authors: Zhang, Qun-Zheng, Li, Zhi-Yuan, Zhang, Le, Lv, Na, Pan, Qing, Ke, Cong-Yu, Zhang, Xun-Li
Format: Article
Language:English
Subjects:
Alkylation
Chemistry
Chemistry and Materials Science
Organic Chemistry
Piperidine
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Summary: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 [(3 S ,5 R )-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 (3 S ,7a R )-3-phenyltetrahydropyrrolo[1,2- c ]oxazol-5(3 H )-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.
ISSN:1070-4280
1608-3393
DOI:10.1134/S1070428020120246