Wednesday, June 25, 2008 Congressional Room (Capital Hilton) 95
Purification Strategies Via Greener Methods for Reductive Amination Reactions Using Resin-Bound Agents
Hephzibah J. Kumpaty, University of Wisconsin - Whitewater, Whitewater, WI
Amine synthesis is an important reaction in drug discovery. One of the key methods for the preparation is via Reductive amination of carbonyl compounds. Reductive amination proceeds through the formation of an imine intermediate upon reaction of a carbonyl compound with primary or secondary amine and is followed by in situ reduction to an amine of higher order. The use of polymer-bound reagents and scavengers provides an attractive alternate approach for integrated organic synthesis and benign purification methods, as the reaction byproducts and excess substrates can be selectively removed from the reaction mixture by simple filtration, thus eliminating the need to use traditional column purification method. We have used polymer-bound reagents to streamline work-up and purification steps in reductive amination reactions. Following reductive amination, crude products were purified by the addition of a catch and release MP-TsOH resin. For catch and release purification, the reaction mixture is filtered and added to MP-TsOH column. This quantitatively ‘catches' the product amine by forming a salt on the resin, allowing suitable removal of non-basic byproducts and starting materials by washing with small amounts of organic solvents. Selective ‘release' of the amine is then effected by addition of a methanolic ammonia solution to the resin.