Synthesis of High Purified Tulobuterol and Its Study of the Organic Impurities

: The synthetic condition of tulobuterol was optimized to gain lower impurity content. Two intermediates were analyzed, and three degradation impurities were isolated using preparative liquid chromatography for the first time and subsequently characterized by various techniques. Possible degradation impurities were deduced by an oxidative mechanism. Two intermediate impurities were detected: α-bromo-2-chloroacetophenone and 1-(2-chlorophenyl)-2-bromoethanol. Three unreported degradation impurities were found and characterized as N-tert-butyl glycine, o-chloro-benzoic acid and chlorobenzene. The single crystal structure of tulobuterol was firstly reported.