A convenient and practical synthesis of imidazol-1-yl-acetic acid hydrochloride was achieved via N-alkylation of imidazole using tert-butyl chloroacetate followed by a non-aqueous ester cleavage of the resulting imidazol-1-yl-acetic acid tert-butyl ester in the presence of titanium tetrachloride. The synthesized imidazol-1-yl-acetic acid hydrochloride was then utilized to prepare zoledronic acid.

This study presents a convenient and practical method for synthesizing imidazol-1-yl-acetic acid hydrochloride, a key intermediate for zoledronic acid, using tert-butyl chloroacetate and titanium tetrachloride.

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Synthesis of imidazol-1-yl-acetic acid hydrochloride: A key intermediate for zoledronic acid

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