(336g) Enable the Implementation of Photochemical Reactions on Commercial Scale Via Using Continuous Flow Reactors

Benzylic bromides represent an important class of building blocks in pharmaceutical industry due to the versatility in the synthesis of active pharmaceutical ingredients. The conventional thermal initiation approach for the synthesis of benzylic bromides via Wohl–Ziegler bromination presents several gaps from sustainability perspective, including the use of harmful chlorinated solvents and explosive radical initiator such as benzoyl peroxide or 2,2'-Azobis(2-methylpropionitrile). Here we present the use of photo chemistry to improve the greenness for this class of reactions by improving the yield and process safety, reducing the Process Mass Intensity (PMI), and eliminating the use of environmentally unfriendly solvents. We also demonstrate the use of continuous flow reactors to address the scaling up challenge associated with the decrease of light intensity along the irradiation path under batch mode. Via using the numbering up approach by the serial connection of continuous photo reaction units, we are able to achieve a productivity of hundreds of 150kg/day under GMP condition.