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“Five or 10 years ago, it would have been very difficult to obtain the required levels,” says Kapa Prasad, distinguished fellow in process R&D at Novartis. “With the combination of methods available and the knowledge that has developed, we can reach those levels routinely.” Although not difficult to carry out, finding the right method is still largely trial and error, Prasad points out.

Prasad and coworker Christine E. Garrett have reviewed what they call “the art of meeting palladium specifications” in active pharmaceutical ingredients (APIs), describing four possible attacks: distillation, adsorption, extraction, and crystallization (Adv. Synth. Catal. 2004, 346, 889). Key to choosing a method, Prasad tells C&EN, “is not adding another operation to a process.” For example, using an adsorbent when there already a filtration step may be fine, but needing to switch solvents to make it work is to be avoided.

A common problem with widely used palladium catalysts, Prasad points out, is that the state of the metal at the end of a reaction is not easily predicted. “In a given reaction all forms could coexist, in which case a single method may not be able to remove everything,” he says. The metal also is expensive, and many researchers want to recover, not just remove, it.




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