An Efficient Catalytic Asymmetric Synthesis of a β2-Amino Acid on Multikilogram Scale

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• 作者：Travis Remarchuk ; Srinivasan Babu ; Jeffrey Stults ; Antonio Zanotti-Gerosa ; Stephen Roseblade ; Shaohui Yang ; Ping Huang ; Chunbo Sha ; Youchu Wang
• 刊名：Organic Process Research & Development
• 出版年：2014
• 出版时间：January 17, 2014
• 年：2014
• 卷：18
• 期：1
• 页码：135-141
• 全文大小：357K
• ISSN：1520-586X

文摘

We describe herein a scalable catalytic asymmetric hydrogenation process for the multikilogram-scale production of a 尾²-amino acid. A short and efficient synthesis of the starting unsaturated N-Boc-protected 尾²-enamide was developed followed by extensive catalysis screening and optimization studies that identified a simple Ru-BINAP catalyst system to directly afford the (S) product in high enantiomeric excess and yield. The final process enabled the multikilogram production in >99% ee, to be used as a key component for one of our clinical candidates.