Asymmetric synthesis of an unnatural α-amino acid, (S)-(+)-3-ethyl norvaline

ORGN 167

Madeline Antane, antanem@wyeth.com, Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543 and Zheng Wang, wangz@wyeth.com, Chemical &Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543.
A practical approach to the asymmetric synthesis of an unnatural a-amino acid, (S)-(+)-3-ethyl norvaline has been developed. A total of 100 g of the amino acid was synthesized with good yield (average ~25% total yield) and high chiral purity (99+% chiral purity). The key chiral center was introduced by Evans' direct azidation method. Longer reaction time and the addition of KOAc gave a higher yield of azidation. Both lithium hydroxide and lithium peroxide gave dominate exocyclic cleavage to produce the desired product.