Novel Method For Palladium Removal

GlaxoSmithKline process chemists have devised a general, low-cost technique for removing residual palladium catalyst from scaled-up drug development reactions (Org. Process Res. Dev., DOI: 10.1021/op800064y). Kae M. Bullock, Mark B. Mitchell, and Jennifer F. Toczko were optimizing a 20-L Suzuki-Miyaura coupling reaction to make a key phenylindole synthetic intermediate, and as is typical in pharmaceutical synthesis, they needed a simple and fast method to obtain high-purity product. The team tried several standard commercially available palladium scavengers such as activated carbon, amine-modified silicas, and trimercaptotriazine. But under their reaction conditions, none of those strategies came close to achieving the 150-ppm palladium target for the crystallized product. The researchers then turned to extraction methods and discovered that adding toluene to the reaction mixture followed by a 20% aqueous sodium bisulfite (NaHSO₃) wash at 60°C reduced the palladium level to 100 ppm. "Here the simple solution gives better results than the established but expensive scavengers," notes Marvin M. Hansen, a research adviser at Eli Lilly & Co. who was asked to comment on the paper. "Based on this research, I think the bisulfite wash should always be tried," he says.