An Integrated Continuous Flow Micro-Total Ultrafast Process System (mu-TUFPS) for the Synthesis of Celecoxib and Other Cyclooxygenase Inhibitors

摘要

Integrated continuous manufacturing has emerged as a promising device for the rapid manufacturing of active pharmaceutical ingredients (APIs). We herein report a newly designed continuous flow micro-total process system platform for the rapid manufacturing of celecoxib, a selective nonsteroidal anti-inflammatory drug. This approach has been proven generally for the synthesis of several alkyl and aryl substituted pyrazoles. In order to minimize the tedious work-up process of potential reaction intermediates/products, we have developed a continuous flow extraction and separation platform to carry out the entire reaction sequence resulting in a short residence time with good yield. The present process was further extended to gram scale synthesis of the COX-2-related API, viz. celecoxib, in the continuous flow process.