Operationally convenient asymmetric synthesis of (S)-2-amino-3,3-bis-(4-fluorophenyl)propanoic acid

This study demonstrated that alkylation of chiral glycine Schiff base 3 with chloride 4 can be efficiently conducted in acetonitrile as a solvent using commercial-grade potassium tert-butoxide as a base. High reaction rate (1 h) chemical (>90%) and stereochemical (>95% de) outcomes of the alkylation step render this procedure reliable and operationally convenient for multi-gram synthesis of enantiomerically pure amino acid 1. Due to the simplicity of experimental procedures and commercial availability all reagents involved, this procedure can be easily reproduced in regular biochemistry laboratories allowing for systematic biological studies and medicinal applications of compound 1.