Stanisław Michałek, Antoni Powała, Lidia Gurba-Bryśkiewicz, Natalia Piórkowska, Patrycja Olejkowska, Abdellah Yamani, Zbigniew Ochal, Krzysztof Dubiel, Maciej Wieczorek
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引用次数: 0
摘要
在我们之前的研究中，我们描述了批量合成CPL304110，一种创新的泛fgfr抑制剂。在此，我们将合成步骤之一的Claisen缩合反应转移到连续流反应器中。通过简单的溶剂转换，将原来的反应时间从20 h缩短到10 min。利用实验方法设计和Statistica®程序，我们优化了反应参数，将反应率从73%提高到84%，反应时间大大缩短(20 h vs 2 min)，生产率提高(74.4 g h−1)，时空产率提高(3720 kg h−1 m−3)。图形抽象
Fast Claisen condensation reaction optimization in a continuous flow reactor
Abstract In our previous study, we described the batch synthesis of CPL304110, an innovative pan-FGFR inhibitor. Herein, we transferred the Claisen condensation reaction, one of the synthesis steps to a continuous flow reactor. A simple solvent switch from ethanol to tetrahydrofuran shortened the original reaction time from 20 h to 10 min. With the use of the design of experiment method and program Statistica ® , we optimized reaction parameters and increased the reaction yields from 73 to 84% with greatly shortened reaction times (20 h vs. 2 min), improved productivity (74.4 g h −1 ), and increased space–time yield (3720 kg h −1 m −3 ). Graphical abstract
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