Pd scavenging after a Suzuki-Miyaura Coupling using a GlaxoSmithKline Published Reaction
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A metal scavenging study was performed following the synthesis of a key synthetic intermediate obtained by the Suzuki-Miyaura coupling presented in scheme below. Various parameters were investigated including the efficiency of SiliaMetS in different formats, scavenging kinetics, intermediate recovery and purity.
Small-Scale Scavenging (Synthesis Scale ~ 5 g)
The table below shows the most efficient SiliaMetS Metal Scavenger products for the treatment of the reaction mixture after work-up in both bulk and fixed-bed mode bed (pre-packed SPE cartridges).
| SiliaMetS Scavenging Efficiency & Intermediate Recovery Results (in %) | ||||
|---|---|---|---|---|
| Scavengers | Batch Reactor Mode (Bulk) | Fixed-Bed Mode (SPE) | Intermediate Recovery | |
| 5 equiv, 4 h, 22°C | 5 equiv, 4 h, 40°C | 6 mL / 1 g | ||
| SiliaMetS Thiol | 95 | > 99 | 98 | > 99 |
| SiliaMetS Thiourea | 83 | 93 | 99 | 98 |
| SiliaMetS Cysteine | 84 | 91 | 97 | > 99 |
| SiliaMetS DMT | 97 | > 99 | > 99 | 98 |
| Initial Pd Concentration | 179 ppm in MTBE | 76 ppm in Toluene | - | |
Scavenging Conclusion
Addition of 5 equivalents of SiliaMetS products for 4 h at the end of the reaction reduces the residual metal concentration to single-digit ppm.Recovery & Purity Conclusion
Palladium was completely removed, while the organic compound was not sequestrated by SiliaMetS products. No impurities were released.
Larger Scale Scavenging (Synthesis Scale ~ 55 g)
SiliaMetS Metal Scavengers in pre-packed SiliaSep Flash Cartridges are a great alternative for metal removal at process development scale. These cartridges offer excellent scavenging efficiency as shown by the results in associated table. After the first run, almost all the palladium was captured. After three runs, less than 1 ppm remained in solution.
| Experimental Conditions | |
|---|---|
| Scavenger Used | SiliaMetS Thiol |
| Cartridge Size | 120 g |
| Nb. Equivalent | 25 equiv |
| Solution Volume | 1 L |
| Flow Rate | 40 mL/min |
| SiliaSep Scavenging Results (in %) | |
|---|---|
| Run # | Scavenging |
| 1 | 97 |
| 2 | 99 |
| 3 | > 99 |
Chemical Development, GlaxoSmithKline, North Carolina, United States
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SiliaMetS Thiol (SH) Metal Scavenger (R51030B)
Our most versatile and robust metal scavenger for a variety of metals under a wide range of conditions. Best scavenger for: Ag, Hg, Os, Pd & Ru. Good scavenger for: Cu, Ir, Pb, Rh, Se & Sn. -
SiliaMetS Thiourea (THU) (R69530B)
SiliaMetS Thiourea (Si-THU) is a versatile metal scavenger for all forms of palladium, and is widely used in the pharmaceutical industry. Once complexed with a transition metal, it has also been reported as being an effective catalyst. Best scavenger for: Pd & Ru. Good scavenger for: Ag, Cu, Fe, Os, Rh, Sc & Sn. -
SiliaMetS DMT (Dimercaptotriazine) (R79030B)
SiliaMetS DMT is the silica - bound equivalent of 2,4,6 - trimercaptotriazine (trithiocyanuric acid, TMT). It is a versatile metal scavenger for a variety of metals and the preferred metal scavenger for ruthenium catalysts and hindered Pd complexes. Best scavenger for: As, Ir, Ni, Os, Pd, Pt, Rh, Ru & Se. Good scavenger for: Cd, Co, Cu, Fe, Sc & Zn. -
SiliaMetS Cysteine (CYS) (R80530B)
SiliaMetS Cysteine (Si-Cys) is the silica bound equivalent of the amino acid Cysteine. It is a versatile metal scavenger for a variety of metals including Pd, Sn, Ru, Pt, Cu, Rh, Cd and Sc under a wide range of conditions and the preferred metal scavenger for tin residues.
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