Impurity formation during drying

A recent paper from workers at GSK describes improvements to the synthesis of Denagliptin (12).  The final chemical step is Boc deprotection of (11) with p-toluenesulphonic acid (p-TSA) in isopropanol (IPA).   Some isolated batches of final product contained impurities 12A (~1%), 12B (~1%), and 12C (~0.3%).  Investigation showed that these three impurities were not produced during the reaction but were produced in the dryer if there was any excess p-TSA in the filter cake during drying.  These impurities could be avoided by washing the filter cake with 2 volumes of IPA prior to drying.


D.E. Paterson,* J.D. Powers, M. LeBlanc, T. Sharkey, E. Boehler, E. Irdam, and M.H. Osterhout (GlaxoSmithKline), Org. Process. Res. Dev., 2009, 13(5), 900-906.