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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
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Diversity-Oriented Synthesis of N,N,O-Trisubstituted Hydroxylamines from Alcohols and Amines by N-O Bond Formation
Jarvis Hill1,2, Asiri A Hettikankanamalage1,2, David Crich1,2,3
1Department of Pharmaceutical and Biomedical Sciences, University of Georgia, 250 West Green Street, Athens, Georgia 30602, United States.
Abstract:
Magnesium dialkylamides react with alcohol-derived 2-methyl-2-tetrahydropyranyl alkyl peroxides (MTHPs) in tetrahydrofuran at 0 °C to give N,N,O-trisubstituted hydroxylamines suitable for medicinal chemistry purposes in good to excellent yields. A wide range of secondary alkyl and aryl amines and primary and secondary alcohol-derived MTHPs are compatible with the described reaction which, coupled with the enormous diversity of commercially available alcohols and secondary amines, suggests broad applicability of the reaction in fragment-based library design.
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