A novel methodology for efficient removal of residual palladium from a product of the Suzuki-Miyaura coupling with polymer-supported ethylenediamine derivatives

In our investigation to efficiently remove residual palladium from a drug candidate prepared via the Suzuki-Miyaura coupling reaction, it was found that polymer-bound ethylene-diamines can absorb both Pd(0) and Pd(II). This property was applied to the removal of residual palladium from the crude 2'-cyanobiphenyl product (R)-2 obtained by the Suzuki-Miyaura coupling of an optically active bromobenzene derivative (R)-1 with a boronate 3. Treatment with the polymer-bound ethylenediamines reduced the palladium content of the crude product from 2000-3000 to 100-300 ppm. Subsequent purification by salt formation with di-p-toluoyl-D-tartaric acid (DTTA) attained a low palladium content of less than 10 ppm.