Continuous Flow Synthesis of Esomeprazole via Asymmetric Sulfoxidation,Organic Process Research & Development

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Continuous Flow Synthesis of Esomeprazole via Asymmetric Sulfoxidation
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2023-05-04 , DOI: 10.1021/acs.oprd.3c00012
Tianxiang Gao ₁ , Jingnan Zhao ₁ , Huinan Sun ₁ , Jianing Li ₁ , Cunfei Ma ₁ , Qingwei Meng _{1,

2}

Affiliation

In this paper, an expeditious and efficient continuous flow process for the synthesis of esomeprazole is described. The asymmetric sulfoxidation was achieved in optimized continuous reaction equipment under a mild condition to provide esomeprazole in 98% yield and 98% ee. For a more efficient reaction, an inert gas was introduced into the homogeneous reaction process, and the residence time in the flow system was markedly reduced (from 2 h in batch to 48 s in flow) because of an enhanced mixing effect. The effects of the reaction equipment, gas and liquid flow rate, reagent equivalents, reaction temperature, system concentration, solvent, and pressure have been investigated successively. To reveal the versatility and applicability of the reaction procedure, a scale-up strategy of continuous oxidation was employed to obtain nearly 20 g of product with a total productivity of 5.6 g/h. Ultimately, esomeprazole sodium was obtained with 99.8% purity and 99.6% ee following a simplified salt formation operation.

中文翻译：

不对称磺化氧化连续流合成埃索美拉唑

本文描述了一种快速高效的连续流程合成埃索美拉唑的方法。在优化的连续反应设备中，在温和的条件下实现不对称磺氧化反应，得到埃索美拉唑，收率98%，ee 98%。为了更有效地进行反应，在均相反应过程中引入了惰性气体，并且由于增强的混合效果，在流动系统中的停留时间显着减少（从间歇式的2小时到流动式的48秒）。先后考察了反应设备、气液流量、试剂当量、反应温度、体系浓度、溶剂和压力的影响。为了揭示反应过程的多功能性和适用性，采用连续氧化放大策略，获得了近 20 克产物，总产率为 5.6 克/小时。最终，经过简化的成盐操作，获得了纯度为99.8%、ee 99.6%的埃索美拉唑钠。

更新日期：2023-05-04

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