Design, Development, and Scale-Up of a Selective meso-Epoxide Desymmetrization Process
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- 作者：David L. Varie ; Christopher Beck ; Sandra K. Borders ; Molly D. Brady ; Jason S. Cronin ; Tracy K. Ditsworth ; David A. Hay ; David W. Hoard ; Richard C. Hoying ; Ryan J. Linder ; Richard D. Miller ; Eric D. Mo
- 刊名：Organic Process Research & Development
- 出版年：2007
- 出版时间：May 2007
- 年：2007
- 卷：11
- 期：3
- 页码：546 - 559
- 全文大小：267K
- 年卷期：v.11,no.3(May 2007)
- ISSN：1520-586X
文摘
A pilot-plant scale desymmetrization of the cyclic meso-epoxide4b, using a chiral lithium amide prepared from symmetricaldiamine 17, was designed and implemented to provide allylicalcohol 3b in high yield and greater than 99% ee. This chiralalcohol was converted to ketone 2b, a key intermediate in anew asymmetric synthesis of LY459477. Chiral diamine 17 wasprepared from a readily available chiral precursor, (R)-
-methylbenzylamine, and could be recovered from the reactionmixture and reused. Studies performed to probe the mechanismof the rearrangement reaction of epoxide 4b showed thatdiamine 17 provided an optimal combination of selectivity andscaleability for this process.
-methylbenzylamine, and could be recovered from the reactionmixture and reused. Studies performed to probe the mechanismof the rearrangement reaction of epoxide 4b showed thatdiamine 17 provided an optimal combination of selectivity andscaleability for this process.