Three-Step Continuous Flow Synthesis of the Intermediate 4-Fluoro-2-methoxy-5-nitrophenol of Linzagolix
4-Fluoro-2-methoxy-5-nitrophenol is a key intermediate of the GnRH receptor antagonist Linzagolix. The traditional synthetic methods have several disadvantages including prolonged reaction time and safety issues. Herein, we describe a three-step continuous flow synthesis of 4-fluoro-2-methoxy-5-nitrophenol via esterification, nitration, and hydrolysis. The total residence time was 234 s, and the total yield was 85.6%, which substantially reduced the reaction time and considerably improved the process safety as well as the total yield.
Authors
- Yu Xia (ORCID: https://orcid.org/0000-0001-5248-9870)
- Yiyang Dong (ORCID: https://orcid.org/0000-0003-1752-3935)
- Xiaoming Zha (ORCID: https://orcid.org/0000-0003-1430-4067)
- Fawen Wu (ORCID: https://orcid.org/0000-0002-6980-191X)
- Tengfei Gong
- Fei Ji (ORCID: https://orcid.org/0000-0003-3778-9028)
- Yang Shi (ORCID: https://orcid.org/0000-0001-6734-6637)
Institutions
- China Pharmaceutical University (CN)
Publication Details
- Journal
- Organic Process Research & Development
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1021/acs.oprd.4c00405
- Citations
- 4
- Primary Topic
- Chemical synthesis and alkaloids
- Type
- article
- Field-Weighted Citation Impact
- 1.00
Funders
- Qinglan Project of Jiangsu Province of China
- National College Students Innovation and Entrepreneurship Training Program