(381ao) Study on the Crystallization Process of Tazobactam Intermediate

Li Huimei,Sun Hua,Han Yiman,Liu Baoshu＊

College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, Hebei 050018, People’s Republic of China

Abstract: Tazobactam is a β-lactamase inhibitor. The synthesis step is up to ten steps, and the purification process is carried out during the preparation of various intermediates. The purification method used is recrystallization. For instance, in the preparation of intermediate 6α-bromopentanoic acid sulfoxide of tazobactam, the purity and yield of the product are improved by exploring the recrystallization process. The factors such as product dissolution temperature, cooling temperature, reverse solvent drop rate, primary crystallization and secondary crystallization were investigated systematically. Ultrasonic technology is also used to solve the solubility of drugs that are difficult to dissolve and the stability of heat-stable drugs, improve the dissolution rate and the number of dissolutions, and comprehensively study the quality, yield and process indicators of the products. For example, in the preparation of an intermediate pyrolysis ring-opening of tazobactam, the phenomenon of oil formation is solved by improving the solvent and using ultrasonic technology. This further increases the purity and yield of the product.

Key words: Tazobactam, recrystallization, ultrasound technique.