This article developed a microreactor system for the continuous synthesis of Pregabalin. Due to the exceptional heat transfer and mixing capabilities exhibited by the system at the microscale, the Hofmann rearrangement reaction, traditionally requiring multiple sequential steps in batch reactors, can now be efficiently achieved in a consolidated single-step microreactor process. The reaction was executed at a comparatively elevated temperature range of 40–50 °C, and took 5–6 min to achieve the yield of over 90 %, which was a significant improvement compared to the conventional batch reactor method, requiring 7–8 h with a yield of 83 %. The microreactor system utilized its excellent mass and heat transfer performance to reduce the level of the key impurity to below 0.15 % at higher reaction temperatures, meeting the quality requirements for pharmaceutical production. Through experimental research, we determined the effects of reaction conditions like concentration, temperature, and residence time on the reaction rate, as well as key trace impurities.

中文翻译：

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使用连续流动系统进行杂质控制的普瑞巴林的高效合成


本文开发了一种用于连续合成普瑞巴林的微反应器系统。由于该系统在微尺度上表现出卓越的传热和混合能力，传统上需要在间歇式反应器中进行多个连续步骤的霍夫曼重排反应现在可以在统一的单步微反应器过程中有效地实现。该反应在40-50℃的较高温度范围内进行，只需5-6分钟，收率即可达到90%以上，与传统间歇式反应器方法（需要7-8小时）相比，这是一个显着的改进。收率83%。微反应器系统利用其优异的传质和传热性能，在较高的反应温度下将关键杂质含量降低至0.15%以下，满足药品生产的质量要求。通过实验研究，我们确定了浓度、温度和停留时间等反应条件对反应速率以及关键痕量杂质的影响。