Practical Synthesis of 1-Aryl-6-(hydroxymethyl)-2-ketopiperazines via a 6-exo Amide-Epoxide Cyclization

…, PG Blazecka, DD Holsworth, JJ Edmunds

Index: Powell, Noel A.; Ciske, Fred L.; Clay, Emma C.; Cody, Wayne L.; Downing, Dennis M.; Blazecka, Peter G.; Holsworth, Daniel D.; Edmunds, Jeremy J. Organic Letters, 2004 , vol. 6, # 22 p. 4069 - 4072

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Citation Number: 8

Abstract

Although the above synthesis satisfied our needs during the early stages of the project, the starting materials proved to be cost prohibitive and of low atom efficiency for synthesis of multigram quantities of 1. To achieve a more practical synthesis, we chose to investigate an alternative retrosynthesis that formed the ketopiperazine ring at the N1−C6 bond through an intramolecular 6-exo cyclization of amide−epoxide 9 (Figure 1). Further retrosynthetic cleavage of the N4−C5 bond ...