Ir/SpiroPAP Catalyzed Asymmetric Hydrogenation of a Key Intermediate of Montelukast: Process Development and Potential Impurities Study

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• 作者：Guo-Liang Zhu ; Xiang-Dong Zhang ; Li-Jun Yang ; Jian-Hua Xie ; Da-Qing Che ; Qi-Lin Zhou ; Pu-Cha Yan ; Yuan-Qiang Li
• 刊名：Organic Process Research & Development
• 出版年：2016
• 出版时间：January 15, 2016
• 年：2016
• 卷：20
• 期：1
• 页码：81-85
• 全文大小：264K
• ISSN：1520-586X

文摘

An efficient and robust process for the asymmetric hydrogenation of a key intermediate of Montelukast using the highly efficient and selective chiral spiro catalyst Ir/SpiroPAP is reported. The developed process was conducted at mild reaction temperature (30 °C) under a hydrogen pressure of 20 atm with low catalyst loading (S/C = 30?000) and afforded the desired chiral alcohol intermediate in 99.5% ee. This process currently has been carried out at 30 kg scale. The process-related impurities (impurities I–V) were also identified, synthesized, and characterized by LC-MS and NMR techniques.