An Efficient Catalytic Asymmetric Synthesis of a beta(2)-Amino Acid on Multikilogram Scale

作者：Remarchuk Travis^*; Babu Srinivasan; Stults Jeffrey; Zanotti Gerosa Antonio; Roseblade Stephen; Yang Shaohui; Huang Ping; Sha Chunbo; Wang Youchu

来源：Organic Process Research & Development, 2014, 18(1): 135-141.

DOI：10.1021/op4002966

We describe herein a scalable catalytic asymmetric hydrogenation process for the multikilogram-scale production of a beta(2)-amino acid. A short and efficient synthesis of the starting unsaturated N-Boc-protected beta(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.

• 出版日期2014-1