A novel reaction cascade leading to a spontaneous intramolecular dipolar cycloaddition through simultaneous generation of 1,3-dipole and dipolarophile

Kalyanam, N.; Rapole, Keshav R.; Ramanujam, Rajendran; Majeed, Muhammed

doi:10.1016/j.tetlet.2013.07.009

Cited by 5 publications

(1 citation statement)

References 14 publications

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“…The protection protocol was adapted from previously described procedures. , A dry 2 L round-bottom flask with magnetic stirring bar was charged with ( S )-methyl 2,5-diaminopentanoate dihydrochloride (25.0 g, 114 mmol) and 4-chlorobenzaldehyde (24.2 g, 240 mmol), sealed, and flushed with argon three times. Anhydrous dichloromethane (750 mL) was added and then stirred.…”

Section: Methodsmentioning

confidence: 67%

Scalable Continuous Flow Process for the Synthesis of Eflornithine Using Fluoroform as Difluoromethyl Source

Köckinger

Hone

Gutmann

et al. 2018

Org. Process Res. Dev.

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The development of a scalable telescoped continuous flow procedure for difluoromethylation of a protected amino acid with fluoroform (CHF 3 , 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 (CHClF 2 , 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.

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Section: Methodsmentioning

confidence: 67%