A new strategy for regiospecific imidazole alkylation of suitably protected histidines is described wherein a phenacyl group serves as a protecting group of the distal imidazole nitrogen atom. Alkylation of N-BOC-1-phenacyl-L-histidine methyl ester at N (3), followed by reductive removal of the phenacyl group from N (1) of the resulting imidazolium intermediate with zinc and acetic acid offers an efficient and flexible route to 3-substituted L-histidines.
![Methyl (S)-5,6,7,8-tetrahydro-5-oxoimidazo[1,5-c]pyrimidine-7-carboxylate Structure](https://image.chemsrc.com/caspic/208/69614-04-6.png)
