Scalable Continuous Flow Process for the Synthesis of Eflornithine Using Fluoroform as Difluoromethyl Source
| Autor: | Bernhard Gutmann, C. Oliver Kappe, Paul Hanselmann, Christopher A. Hone, Michael Bersier, Ana Torvisco, Manuel Köckinger |
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| Rok vydání: | 2018 |
| Předmět: |
Active ingredient
Materials science Fluoroform 010405 organic chemistry Continuous flow business.industry Organic Chemistry Chlorodifluoromethane 010402 general chemistry 01 natural sciences 0104 chemical sciences chemistry.chemical_compound chemistry Eflornithine Side product Scalability medicine Physical and Theoretical Chemistry Process engineering business Global-warming potential medicine.drug |
| Zdroj: | Organic Process Research & Development. 22:1553-1563 |
| ISSN: | 1520-586X 1083-6160 |
| DOI: | 10.1021/acs.oprd.8b00318 |
| Popis: | The development of a scalable telescoped continuous flow procedure for difluoromethylation of a protected amino acid with fluoroform (CHF3, R-23) gas and subsequent high temperature deprotection to provide eflornithine, an important Active Pharmaceutical Ingredient (API), is described. Eflornithine is used for the treatment of sleeping sickness and hirsutism, and it is on the World Health Organization’s list of essential medicines. Fluoroform is produced in large quantities as a side product in the manufacture of polytetrafluoroethylene (PTFE, Teflon). Fluoroform is an ozone-benign and nontoxic gas, but its release into the environment is forbidden under the Kyoto protocol owing to its high global warming potential. The existing manufacturing route to eflornithine uses chlorodifluoromethane (CHClF2, R-22) which will be phased out under the Montreal protocol; therefore, the use of the fluoroform presents a viable cost-effective and more sustainable alternative. The process parameters and equipment setup we... |
| Databáze: | OpenAIRE |
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