Development of a Continuous Flow Process for the Efficient Preparation of Anti-Tuberculosis-Specific Drug TBAJ-876

作者：Feng Gao, Jing Li, Guowei Zhang, Wenting Gu, Zhenfeng Zhang, Zhiqing Liu, Wanbin Zhang · 发表于：Organic Process Research & Development · 年份：2024 · DOI：10.1021/acs.oprd.3c00415 · 被引用次数：8 · 研究领域：Innovative Microfluidic and Catalytic Techniques Innovation、Chemical Synthesis and Analysis、Asymmetric Hydrogenation and Catalysis

Previously, the first asymmetric synthesis of anti-tuberculosis agent TBAJ-876 had been successfully achieved using a synergistic Li/Li catalysis approach, yielding excellent results on a 5 g scale. However, scaling up the process presents significant challenges due to its poor repeatability and safety concerns associated with the commercial scale use of organolithium reagents. In this paper, we describe the design, development, and scale-up of a continuous flow process for the synthesis of TBAJ-876. Notably, our continuous process not only allowed us to synthesize TBAJ-876 at a 100 g reaction scale, an achievement unattainable through batch processing, but it also significantly reduced the reaction time, ensuring robustness, efficiency, and scalability. This method provides a viable pathway for the large-scale industrial production of compounds, such as TBAJ-876.