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

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