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The design of experiments (DoE) in optimization of an aerobic flow Pd-catalyzed oxidation of alcohol towards an important aldehyde precursor in the synthesis of phosphatidylinositide 3-kinase inhibitor (CPL302415)†
Lidia Gurba-Bryśkiewicz,Wioleta Maruszak,Marcin Zagozda,Anna M. Maj,Zbigniew Ochal,Krzysztof Dubiel,Maciej Wieczorek
RSC Advances Pub Date : 11/23/2022 00:00:00 , DOI:10.1039/D2RA07003K
Abstract

Herein, we describe the development of a green, scalable flow Pd-catalyzed aerobic oxidation for the key step in the synthesis of CPL302415, which is a new PI3Kδ inhibitor. Applying this environmental-friendly, sustainable catalytic oxidation we significantly increased product yield (up to 84%) and by eliminating of workup step, we improved the waste index and E factor (up to 0.13) in comparison with the stoichiometric synthesis. The process was optimized by using the DoE approach.

Graphical abstract: The design of experiments (DoE) in optimization of an aerobic flow Pd-catalyzed oxidation of alcohol towards an important aldehyde precursor in the synthesis of phosphatidylinositide 3-kinase inhibitor (CPL302415)
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