Monoselective N-Methylation of Amides, Indoles, and Related Structures Using Quaternary Ammonium Salts as Solid Methylating Agents
Johanna Templ, Edma Gjata, Filippa Getzner, Michael Schnürch
Abstract
We herein report the use of phenyl trimethylammonium iodide (PhMe3NI) as a safe, nontoxic, and easy-to-handle reagent for an absolutely monoselective N-methylation of amides and related compounds as well as for the N-methylation of indoles. In addition, we expanded the method to N-ethylation using PhEt3NI. The ease of operational setup, high yields of ≤99%, high functional group tolerance, and especially the excellent monoselectivity for amides make this method attractive for late-stage methylation of bioactive compounds.
Topics & Concepts
MethylationChemistryReagentMethyl iodideAmmoniumIodideCombinatorial chemistryOrganic chemistryFunctional groupAmideIndole testBiochemistryGenePolymerAsymmetric Hydrogenation and CatalysisChemical Synthesis and AnalysisCarbon dioxide utilization in catalysis