Safe and EfficientContinuous Flow Synthesis of (3<i>S</i>,4<i>S</i>)‑3-[(<i>R</i>)‑1‑(<i>t</i>‑Butyldimethylsilyloxy)ethyl]-4-[(<i>R</i>)‑1-carboxyethyl]-2-azetizinonevia Vertical Dynamic Reactor

The H₂O₂-mediated cleavage of chiral auxiliary as a mild and selective method is commonly used in the pharmaceutical industry but they can also introduce unexpected safety hazards due to the O₂ release. Here, a novel safe and efficient continuous flow synthesis process for (3<i>S</i>,4<i>S</i>)-3-[(<i>R</i>)-1-(<i>t</i>-butyldimethylsilyloxy)ethyl]-4-[(<i>R</i>)-1-carboxyethyl]-2-azetizinone (<b>4-BMA</b>), a key intermediate of meropenem was reported. The vertical dynamic reactor (<b>VDR</b>) effectively addresses the safety risk by preventing electrostatic accumulation and eliminating gas-phase space within the reactor. Compared to the current batch process, the continuous flow synthesis method reported in this paper not only significantly improved the safety of the process but also greatly shortened the reaction time (from 600 to 20 min) and increased the yield (from 85 to 91%) due to its high mass and heat transfer efficiency. These results indicated that the <b>VDR</b> provides great potential for the industrial scale-up of <b>4-BMA</b>.