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Fully Continuous Flow Synthesis of 3-Chloro-4-oxopentyl Acetate: An Important Intermediate for Vitamin B1
Organic Process Research & Development ( IF 3.4 ) Pub Date : 2021-08-27 , DOI: 10.1021/acs.oprd.1c00065
Meifen Jiang 1 , Minjie Liu 2 , Chao Yu 2 , Dang Cheng 1 , Fener Chen 1
Affiliation  

A fully continuous flow synthesis of 3-chloro-4-oxopentyl acetate (2), an important intermediate for vitamin B1 (1), was developed. This continuous flow manufacturing included two chemical transformations and an inline extraction step without intermediate purification and solvent exchange. In this work, the traditional synthetic route for batch operation was efficiently simplified via a series of separated screening tests in flows under various conditions. We found that the chlorination reaction can be carried out in only 30 s at room temperature by flow. We also simplified the decarboxylation/acylation step by using a cross-mixer, so that acetic anhydride was no longer required in the acylation reaction. A computational fluid dynamics simulation was carried out to study the improved micromixing of liquid–liquid two-phase streams. Finally, 3-chloro-4-oxopentyl acetate (2) was obtained in a 90% isolated yield with a product purity of 96% and a total residence time of approximately 32 min. This fully continuous process was operated smoothly for 12 h, and approximately 19.1 g of the desired product was generated with a production rate of 1.79 g h–1.

中文翻译:

3-Chloro-4-oxopentyl Acetate 的全连续流合成:维生素 B1 的重要中间体

3-氯-4-氧代戊基乙酸酯 ( 2 )的完全连续流动合成,它是维生素 B 1的重要中间体( 1), 已开发。这种连续流制造包括两个化学转化和一个在线提取步骤,没有中间纯化和溶剂交换。在这项工作中,通过在各种条件下进行的一系列分离筛选测试,有效地简化了批量操作的传统合成路线。我们发现氯化反应可以在室温下通过流动在30 s内进行。我们还通过使用交叉混合器简化了脱羧/酰化步骤,因此酰化反应中不再需要乙酸酐。进行了计算流体动力学模拟以研究改进的液-液两相流的微混合。最后,3-chloro-4-oxopentyl acetate ( 2) 以 90% 的分离产率获得,产品纯度为 96%,总停留时间约为 32 分钟。这种完全连续的过程平稳运行了 12 小时,以 1.79 gh –1的生产率生产了大约 19.1 g 所需产品。
更新日期:2021-09-17
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