Synthesis of heterocyclic β-amino acids. A convenient preparation of β-amino-5-pyrimidinepropanoic acid and derivatives

Abstract The novel (2E)-1,1-dimethylethyl-3-(5-pyrimidinyl)-2-propenoate 3 , obtained by Heck coupling between 5-bromopyrimidine and tert -butyl acrylate undergoes nearly quantitative Michael addition in t-butanol saturated with ammonia to the hitherto unknown β-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 amino acid 7 is described. The tert -butyl ester 4 and the N-protected β-amino acid 7 are useful in peptide and peptidomimic synthesis.