Solvent-free synthesis for imidazole-1-yl-acetic acid hydrochloride: an intermediate for zoledronic acid

In the present work, a convenient and environmentally-friendly protocol for the preparation of imidazol-1-yl-acetic acid hydrochloride is discussed via solvent-free N-alkylation of imidazole by tert-butyl chloroacetate, the obtained imidazol-1-yl-acetic acid tert-butyl ester was hydrolyzed in water and treated with hydrochloric acid to obtain the imidazol-1-yl-acetic acid hydrochloride in good yields. Unlike the previously reported methods, this two step process was completely free from the use of hazardous solvents. In addition, it revealed high yield and characterized using a simple and easy work-up procedure. The imidazol-1-yl-acetic acid hydrochloride that produced in this study was converted into zoledronic acid monohydrate, which can be utilized in medicinal aplications.