70471-10-2Relevant academic research and scientific papers
Scalable Continuous Flow Process for the Synthesis of Eflornithine Using Fluoroform as Difluoromethyl Source
K?ckinger, Manuel,Hone, Christopher A.,Gutmann, Bernhard,Hanselmann, Paul,Bersier, Michael,Torvisco, Ana,Kappe, C. Oliver
, p. 1553 - 1563 (2018)
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 were optimized on laboratory scale for the two reaction steps to improve product yield and scalability. The telescoped flow process utilizing fluoroform gas was operated for 4 h to afford the target molecule in 86% isolated yield over two steps with a throughput of 24 mmol/h.
METHOD FOR PREPARATION OF DIFLUOROMETHYLORNITHINE
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Page/Page column 23-24, (2019/04/16)
The invention discloses a method for preparation of protected difluoromethylornithine by a difluoromethylation of dibenzaldimine ornithine ester using CHF3 and LiHMDS (lithium bis(trimethylsilyl)amide), which can be converted to a salt of unprotected difl
