Масштабований синтез 4-функціоналізованих ізоксазолідинів та піразолідинів

• Date: 2026
• Main Authors: Kaliberda, Oleksandr V., Zarudnitskii, Evgenij V.
• Format: Article
• Language: English
• Published: National University of Pharmacy 2026
• Subjects: синтез; ізоксазолідин; піразолідин; масштабування; функціоналізація
• Online Access: https://ophcj.nuph.edu.ua/article/view/353295
• Journal Title: Journal of Organic and Pharmaceutical Chemistry

A practical and scalable cyclization method for the preparation of C4-functionalized isoxazolidine and pyrazolidine building blocks is described. The methodology is based on the use of commercially available 1,3-dihalide and protected hydroxylamine or hydrazine derivatives under unified NaH/DMF conditions, enabling direct assembly of both N,O- and N,N-heterocycles. The process is operationally robust and successfully implemented on an over 100 g scale. The oxidative conversion of exocyclic alkene intermediates made it possible to obtain isoxazolidin-4-one and pyrazolidin-4-one scaffolds. The resulting pyrazolidine derivatives demonstrate a broad tolerance to reductive and oxidative conditions, whereas isoxazolidines exhibit certain stability limitations. The combination of the modular C4 diversification, orthogonal nitrogen protection, and preparative scalability transforms these saturated heterocycles into practically accessible building blocks for medicinal chemistry applications.