Synthesis Of Heterocyclic Beta-Amino Acids - A Convenient Preparation Of Beta-Amino-5-Pyrimidinepropanoic Acid And Derivatives

The novel (2E)-1,1-dimethylethyl-3-(5-pyrimidinyl)-2-propenoate 3, obtained by Heck coupling between 5-bromapyrimidine and tert-butyl acrylate undergoes nearly quantitative Michael addition in t-butanol saturated with ammonia to the hitherto unknown beta-amino-5-pyrimidinepropanoic ester 4. The synthetic utility of this reactions sequence is demonstrated by preparation of 4 on a multigram scale. The transformation of the ester to the free amino acid 5 and to the Cbz-N-protected aminoacid 7 is described. The tert-butyl ester 4 and the N-protected beta-amino acid 7 are useful in peptide and peptidomimic synthesis.