Design, Development, and Scale-Up of a Selective meso-Epoxide Desymmetrization Process

Autor:	Moher Eric D, John Allan Rieck, Richard D. Miller, Tracy K. Ditsworth, David A. Hay, Sandra S. K. Borders, Mindy B. Forst, Richard C. Hoying, and Duane A. Pierson, Joseph A. Turpin, Varie David Lee, Ryan J. Linder, Jason S. Cronin, David D. Anderson, and Jacob R. Remacle, Molly D. Brady, Hoard David W, Paul N. Dodson, Christopher A. Beck
Rok vydání:	2007
Předmět:	chemistry.chemical_classification Ketone Lithium amide Organic Chemistry Enantioselective synthesis Epoxide Desymmetrization chemistry.chemical_compound chemistry Diamine Organic chemistry Rearrangement reaction Physical and Theoretical Chemistry Selectivity
Zdroj:	Organic Process Research & Development. 11:546-559
ISSN:	1520-586X 1083-6160
Popis:	A pilot-plant scale desymmetrization of the cyclic meso-epoxide 4b, using a chiral lithium amide prepared from symmetrical diamine 17, was designed and implemented to provide allylic alcohol 3b in high yield and greater than 99% ee. This chiral alcohol was converted to ketone 2b, a key intermediate in a new asymmetric synthesis of LY459477. Chiral diamine 17 was prepared from a readily available chiral precursor, (R)-α-methylbenzylamine, and could be recovered from the reaction mixture and reused. Studies performed to probe the mechanism of the rearrangement reaction of epoxide 4b showed that diamine 17 provided an optimal combination of selectivity and scaleability for this process.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::f53e1e122ffede3fb8c73298de6793ee https://doi.org/10.1021/op060225f Zobrazit plný text záznamu