A simple and widely applicable technique to avoid precipitation-induced clogging in continuous-flow processes involving gas and liquid reagents (such as hydrogenations) has been developed. Management of solid compounds poses one of the largest scale-up risks in the flow manufacturing of pharmaceuticals and fine chemicals. As noted in this study, compounds with limited solubility in low-boiling solvents can be susceptible to precipitation when mixed with a gas stream in a standard tee-mixer. The prescribed technique, whereby the gas stream is prewetted with a solvent prior to contacting with the feed solution, has been successfully applied both in lab and scale-up platforms to enhance the stable (clog-free) operating run time of continuous-flow synthesis of an active pharmaceutical ingredient (API) intermediate from minutes to days.

中文翻译：

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解决 API 中间体连续流加氢合成中气液混合引起的堵塞问题


已经开发了一种简单且广泛适用的技术，以避免在涉及气体和液体试剂（如加氢）的连续流过程中发生沉淀引起的堵塞。固体化合物的管理是药品和精细化学品流产中最大的放大风险之一。如本研究所述，在低沸点溶剂中溶解度有限的化合物在与标准 T 形混合器中的气流混合时，可能容易沉淀。在与进料溶液接触之前，用溶剂预润湿气流的处方技术已成功应用于实验室和放大生产平台，可将活性药物成分 （API） 中间体连续流合成的稳定（无堵塞）运行时间从几分钟提高到几天。