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)

• Stanisław Michałek^a,b
• Lidia Gurba-Bryśkiewicz^a
• Wioleta Maruszak^a
• Marcin Zagozda^a
• Anna M. Maj^a
• Zbigniew Ochal^b
• Krzysztof Dubiel^a
• Maciej Wieczorek^a

• ^aCelon Pharma S.A., Ul. Marymoncka 15, 05-152 Kazuń Nowy, Poland
• ^bFaculty of Chemistry, Warsaw University of Technology, Ul. Noakowskiego 3, 00-664 Warsaw, Poland

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.

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