Transition Metal Removal on Large Scale: Deloxan Resin

Posted 2021-05-10 有机合成与工艺文献分享

Deloxan resins are macroporous organofunctional polysiloxane beads containing N,N’-disubstituted thiourea or thiol groups that can be employed for the removal of a large number of metals such as Pd, Pt, Ru, Ir, Rh, Ag, Au, Zn,Cu(I), Cu(II), Fe(III), Cd, Hg, and Pb.

Deloxan THP has also been employed by the process group at Pfizer to scavenge both Pd and Cu after the Sonogashira coupling between aryl iodide 107and 3-butyn-1-ol (104) to generate tricyclic intermediate 108 during the synthesis of pyrrolquinolone 109, a compound with promising activity against herpes virus DNA polymerases.

                           

◆Crude 108 contained 242 ppm Pd and 105 ppm Cu and an extensive screen of conditions for their removal was implemented.

◆Thus, TMT, Amberlite IRC resins,ammonium formate, 2-hydroxypyridine, silica gel, and dimethylaminoethanethiol proved ineffective to reduce the levels of both metals.

◆An alumina plug or either 1,2-bis(diphenylphosphino)ethane or 1,3-bis(diphenylphosphino)propanereduced considerably the metal content but the phosphines did not perform well on crude mixtures.

◆It was finally found that extracting 108 into aqueous HCl and treating this solution with Deloxan THP(80wt%) at rt overnight reduced both Pd and Cu to acceptable levels.

After filtration and basification with Na2CO3, 108 was extracted into CH2Cl2 and crystallized from MTBE/MeCN in 60% yield with 20ppm Pd and 2ppm Cu.