1. Implementation of micelle-enabled C(sp2)–C(sp3) cross-electrophile coupling in pharmaceutical synthesis.
- Author
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Wu, Bin, Ye, Ning, Zhao, Kangming, Shi, Min, Liao, Jiayu, Zhang, Jing, Chen, Wei, Li, Xianzhong, Han, Yufeng, Cortes-Clerget, Margery, Regnier, Morgan Louis, Parmentier, Michael, Mathes, Christian, Rampf, Florian, and Gallou, Fabrice
- Subjects
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APROTIC solvents , *ELECTROPHILES , *POLAR solvents , *COPPER , *CATALYSIS - 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). [ABSTRACT FROM AUTHOR]
- Published
- 2024
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