Process Development and Pilot-Plant Synthesis of (S)-tert-Butyl 1-Oxo-1-(1-(pyridin-2-yl)cyclopropylamino)propan-2-ylcarbamate: Studies on the Scale-Up of Kulinkovich鈥揝zymoniak Cycloprop
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- 作者：Wenjie Li ; Joe J. Gao ; Jon C. Lorenz ; Jinghua Xu ; Joe Johnson ; Shengli Ma ; Heewon Lee ; Nelu Grinberg ; Carl A. Busacca ; Bruce Lu ; Chris H. Senanayake
- 刊名：Organic Process Research & Development
- 出版年：2012
- 出版时间：May 18, 2012
- 年：2012
- 卷：16
- 期：5
- 页码：836-839
- 全文大小：191K
- 年卷期：v.16,no.5(May 18, 2012)
- ISSN：1520-586X
文摘
A practical and scalable synthesis of (S)-tert-butyl 1-oxo-1-(1-(pyridin-2-yl)cyclopropylamino)propan-2-ylcarbamate, an intermediate in the manufacture of a lymphocyte function-associated antigen 1 inhibitor, is described. The titled compound is prepared via an efficient one-pot, two-step telescoped sequence starting from readily available materials. A modified Kulinkovich鈥揝zymoniak cyclopropanation of a nitrile followed by in situ amide formation with an activated carboxylic acid derivative afforded the target product in about 50% overall isolated yield and >97% purity.