Citation: Hui Jin, Qin Cai, Peiwen Liu, Yan Chen, Derong Wang, Weiping Zhu, Yufang Xu, Xuhong Qian. Multistep continuous flow synthesis of Erlotinib[J]. Chinese Chemical Letters, ;2024, 35(4): 108721. doi: 10.1016/j.cclet.2023.108721 shu

Multistep continuous flow synthesis of Erlotinib

State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

wpzhu@ecust.edu.cn

xhqian@ecust.edu.cn

Received Date: 12 April 2023
Revised Date: 4 June 2023
Accepted Date: 21 June 2023
Available Online: 22 June 2023

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Erlotinib is an orally administered, highly effective, specific epidermal growth factor receptor tyrosine kinase inhibitor, used to treat non-small cell lung cancer and pancreatic cancer. The traditional synthetic methods for Erlotinib exhibit long reaction time and safety concern. Herein, we describe a novel five-step route for the synthesis of Erlotinib in flow. These five steps comprise etherification, nitration, reduction, addition and cyclization reactions. All steps were optimized and converted to continuous flow process, which drastically reduces the reaction time and considerably improves the process safety as well as the total yield. Enabled by five continuous flow units, Erlotinib is efficiently afforded with an E-factor of 38, an overall yield of 83%, and a total residence time of 25.1 min. Majority steps in this process have been optimized for quantitative conversion, which offers the possibility of telescoping the entire process.
- Erlotinib,
- Continuous flow synthesis,
- Microchannel flow reactor,
- Process optimization,
- Continuous nitration,
- Continuous hydrogenation
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