Ultrasound-assisted efficient synthesis of 3-[4-(2-methoxyethyl) phenoxy] propane -1,2 -diol (Metoprolol EP impurity D)

Özet

Safety of a drug molecule is dependent on various impurities formed during chemical process which may cause drug product instability, decreased product performance, loss in potency, and/or formation of potentially genotoxic impurities. Therefore, it is essential to identify and quantify the impurities generated during the drug development stage. Herein, we describe the synthesis and characterization of metoprolol EP Impurity D, 3-[4-(2- methoxyethyl)phenoxy]propane-1,2-diol (1), reported in European Pharmacopeia. The synthesis of compound 1 was accomplished starting from 4-(2-methoxyethyl)phenol in two steps via KOH-mediated substitution with epichlorohydrin and then H2SO4 catalyzed hydrolysis of the formed epoxide.