Multi-step continuous flow synthesis of fluconazole
The development of a flow chemistry approach to the anti-fungal fluconazole is described. A continuous, two-reactor, three-step synthesis of fluconazole from 2-chloro-2′,4′-difluoroacetophenone was achieved with no intermediate purification. The synthesis has been successfully demonstrated on a Vapourtec commercial flow chemistry system.
KeywordsFluconazole Corey-Chaykovsky epoxidation 1,2,4-triazole Friedel-crafts acylation Vapourtec
This research was developed with funding from the Defense Advanced Research Projects Agency (DARPA, W911NF-16-C-0051). The views, opinions, and/or findings expressed are those of the author(s) and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government.
- 1.Becher R, Wirsel SG (2012) Appl Microbiol Biotechnol 95(4):825–840Google Scholar
- 2.Abe F, Usui K, Hiraki T (2009) Biochemistry 48(36):8494–8504Google Scholar
- 3.WHO Model List of Essential Medicines (20th list) http://www.who.int/medicines/publications/essentialmedicines/en/ Retrieved 27 February 2018
- 4.Wang Y, Bian C (2014) Asian J Chem 26(24):8593Google Scholar
- 5.Korwar S, Amir S, Tosso PN, Desai BK, Kong CJ, Fadnis S, Telang NS, Ahmad S, Roper TD, Gupton BF (2017) Eur J Org Chem 6495–6498Google Scholar
- 6.Yang Y, Gong Z, Yang K (2015) Preparation of fluconazole from epoxy chloropropane through addition reaction, oxidation, and Grignard reaction. Patent CN 104557747Google Scholar
- 7.Palomo Coll (1994) A Process for preparation of fluconazole. Patent ES 2049663Google Scholar
- 8.Wu C, Li X, Shi X, Shi Y, Wang M (2011). Zhongguo Yaowu Huaxue Zazhi 21(4):304Google Scholar