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Updated: Jul 4, 2025

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
Implementation of micelle-enabled C(sp2)-C(sp3) cross-electrophile coupling in pharmaceutical synthesis
Bin Wu1, Ning Ye1, Kangming Zhao1
1Chemical & Analytical Development, Suzhou Novartis Technical Development Co., Ltd, Changshu, Jiangsu 215537, China. bin-3.wu@novartis.com.
Abstract:
A sustainable C(sp2)-C(sp3) cross-electrophile coupling was developed between readily available 5-bromophthalide and 1-benzyl-4-iodopiperidine under micellar conditions, leading to a key intermediate of one of our development compounds. Copper was found to play a crucial role as a co-catalyst in this dual catalysis system. The chemistry and process were successfully demonstrated in a kilo scale to deliver sufficient drug substance to the clinical campaigns. This is the first reported scale-up of such a challenging cross-electrophilic coupling that uses an aqueous medium, and not undesirable reprotoxic polar aprotic solvents (e.g. DMF, DMAc, and NMP).
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