Design, development, and scale-up of a selective meso-epoxide desymmetrization process

DL Varie, C Beck, SK Borders, MD Brady…

Index: Varie, David L.; Beck, Christopher; Borders, Sandra K.; Brady, Molly D.; Cronin, Jason S.; Ditsworth, Tracy K.; Hay, David A.; Hoard, David W.; Hoying, Richard C.; Linder, Ryan J.; Miller, Richard D.; Moher, Eric D.; Remacle, Jacob R.; Rieck III, John A.; Anderson, David D.; Dodson, Paul N.; Forst, Mindy B.; Pierson, Duane A.; Turpin, Joseph A. Organic Process Research and Development, 2007 , vol. 11, # 3 p. 546 - 559

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Citation Number: 18

Abstract

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 ...