Potassium isopropyl xanthate (PIX): an ultra-efficient palladium scavenger

The increasing employment of palladium-catalyzed reactions in the synthesis of active pharmaceutical ingredients (APIs) has created a pressing need for ultra-efficient palladium removal of the resulting metal contaminants. This communication discusses the identification and development of Potassium Isopropyl Xanthate (PIX) as a simple, readily available and ultra-efficient palladium scavenger capable of removing residual palladium from the API to levels less than 1 ppm. In addition, the discovery of a synergistic effect of iodine, in combination with PIX and other palladium scavengers, to enhance palladium removal has further increased the efficiency of the palladium removal process. The PIX and I2 system has been successfully applied to the ceftolozane sulfate 2nd generation manufacturing chemistry to reduce palladium in the API resulting from a late stage palladium-catalyzed coupling reaction to only 0.1 ppm.