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Synthesis 2024; 56(05): 821-827
DOI: 10.1055/a-2218-9048
DOI: 10.1055/a-2218-9048
paper
Special Issue Flow Chemistry
One-Flow Operation via 4-Bromopyridine Enables Flash Synthesis of AChE Inhibitor
This work was supported by JSPS KAKENHI Grant Numbers, JP20K15276 (Grant-in-Aid for Early-Career Scientists), JP20KK0121 (Fostering Joint International Research (B)), JP21H01936 (Grant-in-Aid for Scientific Research (B)), JP21H01706 (Grant-in-Aid for Scientific Research (B)), and JP21H05080 (Grant-in-Aid for Transformative Research Areas (B)). This work was also partially supported by AMED (JP21ak0101156), the Core Research for Evolutional Science and Technology (CREST, JPMJCR18R1), New Energy and Industrial Technology Development Organization (NEDO, P19004), the Japan Keirin Autorace Foundation, and the Ogasawara Foundation for the Promotion of Science and Engineering.
Abstract
4-Bromopyridine is a building block that can be converted into valuable compounds, but due to its low stability, it is commercially available in the form of hydrochloride salt. Therefore, the hydrochloride salt is usually desalted with a basic aqueous solution and dried before organic reaction. In this study, to simplify the preparation and reaction procedure of 4-bromopyridine, multiple operations, desalting with a base, separation of the aqueous layer, and subsequent halogen–lithium exchange reaction were integrated into a single flow reaction. The reaction sequence was completed within 20 seconds and the yields were higher than the conventional methods. This is because the subsequent reaction can be performed immediately after the generation of 4-bromopyridine, which is unstable under ambient conditions.
Key words
one flow operation - flow microreactors - flash chemistry - integrated flow reactions - bromopyridine hydrochloride - liquid-liquid separate membrane - AChE inhibitorsSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2218-9048.
- Supporting Information
Publication History
Received: 14 October 2023
Accepted after revision: 28 November 2023
Accepted Manuscript online:
28 November 2023
Article published online:
04 January 2024
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The direct use of arylborates generated in flow microreactors for cross-coupling reactions has been reported, see: