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SiliaMetS® - Customers Successful Stories Published by Customers

SiliaMetS Metal Scavengers are being used by many pharmaceutical companies, which are now using them in pilot plant. In the litterature, you can find some sucessful stories published by customer that highlight the ease of use and reliable performance of SiliaMetS. Some examples are presented in the following pages.

An Amgen Case Study1

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In 2009, Amgen published a chapter in “Catalysis of Organic Reactions” related to the used of scavengers for the removal of palladium in small to multi-kilogram production scale. In their study, they evaluated various parameters such as the scavenging efficiency, the influence of the scavenger loading and the loss of product to adsorption (recovery). The study was made on a palladium catalyzed sulfonamide coupling and scavenger screening was performed at both room temperature and 65°C using 31 different scavengers.

case-study-amgen

Amgen Scavenger Screening Results

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Condition: 20 mg of each scavenger (20% wt) in 2 mL HPLC vial that contains 1 mL of crude reaction mixture containing 100 mg of product. Each vial was sealed and agitated overnight. Initial palladium concentration was 423 ppm.
The BEST scavenger identified during their study was the SiliaMetS Thiourea providing the lowest Pd content (residual palladium concentration: 3 % or < 14 ppm) without product sequestration. They mentioned that SiliaMetS Thiourea was used extensively in early process development work.

case-study-thiourea

1Catalysis of Organic Reactions, Chapter 5. Application of Scavengers for the Removal of Palladium in Small Lot Manufacturing
Allgeier & al., Amgen Inc., Thousand Oaks (California)

Cost Comparison for Most Efficient Scavengers (≥ 80%)

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In pilot-plant scale, the best compromise between the cost per ppm removed and the scavenging efficiency is crucial. The histogram at right shows a cost comparison on best scavengers identified.
Results highlighted by the graph reduced the number of options to only 4 candidates for further evaluation: in pole position the SiliaMetS Thiourea , and then the TMT, TMT-Na3, and the Smopex 234.

most-efficient-metal-scavengers

 

Top 4 scavengers overview

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A screening validation was conducted on 1 g scale purification (10 mL of solution) with 20% w/w of each top 4 scavengers at 65°C overnight. After filtration, residual metal concentration was analyzed by ICP-MS as well as product recovery by HPLC (see table below). SiliaMetS Thiourea was chosen for the large scale purification. See Amgen’s paper for further details.

Screening Validation Results on Top 4 Scavengers
Scavengers Residual Metal Concentration (ppm) Product Recovery Commentary
Screening Exp. in Solution Validation Exp. in Solution Validation Exp. in Solid Product1
SiliCycle Thiourea 14 11 158 102 % Best performance but also most expensive.
TMT 33 15 264 104 % Fine in suspension, filterability concerns on scale.
Smopex 234 36 38 496 84 % Favorable cost but product recovery not satisfied.
TMT-Na3 85 81 1 555 78 % Very basic compounds (not good with base sensitive groups). Low recovery.
Purification Scale: 100 mg 1 g 1 g 1 g  
Initial Concentration: 423 ppm 381 ppm 3 577 ppm    
Note: 1 Solid product refers to dividing the metal concentration in ppm by the amount of product in the test (1g).

Amgen’s Conclusion

“Scavengers offer a practical and expedient option for removing Pd from process streams to ensure quality of organic products... The screening protocol involves treatment of a candidate process stream with 20 % w/w scavenger on product at both room temperature and 65°C followed by analysis of Pd and product adsorption. High-temperature treatment increased the efficiency of Pd removal... Evaluation of process costs is key to identifying Pd removal solutions. While scavengers add cost to a process, their use is often justified by the speed to production in early phase development.

 

An AstraZeneca Case Study

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Publication: Ryberg, P., Organic Process Research & Development, 12 (2008) p.540
  Process Chemistry, AstraZeneca PR&D, Sweden.

In 2008, AstraZeneca published a paper in witch they removed palladium impurities in a large-scale process. The workup method that was found to work the best was a treatment with SiliaMetS Thiol (25 % w/w or ~1.4 kg) at 50°C to purify more than 6.7 kg. Final residual palladium concentration was as low as 1-2 ppm

case-study-astra-zeneca

 

A Pfizer Global R&D Case Study

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Publication: Dorow, R.L. & all, Organic Process Research & Development, 10 (2006) p.493
  Pfizer Global Research and Development, Kalamazoo, Michigan (USA).

In 2006, Pfizer published a paper in witch they removed palladium & copper impurities in a 20 kg pilot plant scale. They made two subsequent treatments using SiliaMetS Thiol (20 % + 7 % w/w) at room temperature for 12 hours. After scavenging with SiliaMetS Thiol, the desired product was obtained with a yield of 76 % and was containing only 17 ppm Pd and 1 ppm Cu. An alternative method was also tried using 80 % w/w of Deloxan THP (Degussa AG) overnight followed by basification with Na2CO3. Residual metal concentration with this method was higher compared to the one withSiliaMetS and the yield was lower (about 60-70 %).SiliaMetS allows lower residual metal concentration & higher yield in less manipulations!

case-study-pfizer

 

An Abbott Laboratories Case Study

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Publication: Ravn, M.M. & all, P., Organic Process Research & Development, 14 (2010) p.417
  Global Pharmaceutical R&D, Process Research & Development and Discovery, Abbott Laboratories, Chicago, Illinois (USA).

In 2010, Abbott Laboratories published a paper in witch they removed palladium and iron impurities using SiliaMetS Thiol (50 % w/w relative to 1). Thus, palladium and iron levels were respectively 6 ppm and 66 ppm. Take a look at Abbott’s publication for more details.

case-study-abbott

 

A Johnson & Johnson Case Study

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Publication: Houpis I.N. & all, Organic Process Research & Development, 13 (2009) p.598
  Johnson & Johnson PRD, API Development, Belgium, and Solvias A.G., Synthesis and Catalysis, Switzerland.

In 2009, J&J in collaboration with Solvias published a paper in witch they developed a mild Sonogashira reaction using various metal catalysts. Treatment with SiliaMetS Thiol removed simultanously Pd, Cu & Al. Residual concentrations were respectively < 50, 10, and 3 ppm, in the isolated product 3. Take a look at J&J’s publication for more details.
Note: copper comes from a previous synthesis step.

case-study-johnson-johnson

 

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  1. SiliaMetS thiol metal scavenger - Best scavenger: Ag, Hg, Os, Pd & Ru - Good scavenger: Cu, Ir, Pb, Rh & Sn

    SiliaMetS® Thiol metal scavenger

    SiliaMetS Thiol is our most versatile and robust metal scavenger for a variety of metals under a wide range of conditions.
  2. SiliaMetS® DEAM

    SiliaMetS® DEAM

    SiliaMetS DEAM is a versatile scavenger designed to remove trace metal or boronic acids from reaction intermediates or final APIs. 

  3. SiliaMetS Novel Scavenger Kit. Includes the following products: AMPA - DEAM - DOTA - DMT - Guanidine - Thiol

    SiliaMetS® Novel Scavenger Kit (K34530B)

    This metal scavenger kit includes the following products: AMPA - DEAM - DOTA - DMT - Guanidine - Thiol
  4. SiliaMetS® AMPA

    SiliaMetS® AMPA

    SiliaMetS AMPA is an aminomethylphosphonic acid ligand known for its excellent metal-bonding properties. It is particularly efficient to remove Aluminium, Antimony, Nickel, Lanthanides, and also very effective for Cobalt, Iron, Manganese and Zinc scavenging from reaction intermediates or final APIs. 

  5. SiliaMetS Tin Metal Scavenger Kit (K34730B) - Includes the following products: Carbonate - Cysteine - DEAM - DMT - TAAcOH - TAAcONa - Thiourea - Thiol

    SiliaMetS® Tin Metal Scavenger Kit (Carbonate; Cysteine; DEAM; DMT; TAAcOH; TAAcONa; Thiol; Thiourea) (K34730B)

    SiliaMetS® Tin Metal Scavenger Kit: Carbonate; Cysteine; DEAM; DMT; TAAcOH; TAAcONa; Thiol; Thiourea
  6. SiliaMetS Palladium Metal Scavenger Kit - Includes: DMT - Diamine - Thiol - Thiourea - Imidazole - Triamine

    SiliaMetS® Palladium Metal Scavenger Kit (K34630B)

    This kit includes the following products : DMT - Diamine - Thiol - Thiourea - Imidazole - Triamine
  7. SiliaMetS DOTA

    SiliaMetS DOTA

    SiliaMetS DOTA is a silica-supported tetracarboxylic acid and its various conjugate bases. DOTA molecule is a well-adopted complexing agent. Linked to various metals, so formed-complexes are used as contrast agents in cancer treatments or other medical applications.
  8. SiliaMetS® Cysteine

    SiliaMetS® Cysteine

    SiliaMetS® Cysteine (Si-Cys) is the silica bound equivalent of the amino acid Cysteine. By attaching the molecule to the backbone via the amino group, the thiol group remains free and accessible for higher metal scavenging efficiency. 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.

  9. SiliaMetS Dimercaptotriazine (DMT) metal scavenger

    SiliaMetS® Dimercaptotriazine (DMT)

    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 (i.e. Pd(dppf)Cl2).
  10. SiliaBond® Amine

    SiliaBond® Amine

    SiliaBond® Amine (Si-NH2) is an effective scavenger of acid chlorides, sulfonyl chlorides, isocyanates and other electrophiles. Si-NH2 has been shown to be effective metal scavenger and catalyst for Knoevenagel reactions. SiliaBond Amine is also used in chromatography as normal phase sorbent.

  11. SiliaBond® Amine nec

    SiliaBond® Amine nec

    SiliaBond® Amine (Si-NH2) is an effective scavenger of acid chlorides, sulfonyl chlorides, isocyanates and other electrophiles. Si-NH2 has been shown to be effective metal scavenger and catalyst for Knoevenagel reactions. SiliaBond Amine is also used in chromatography as normal phase sorbent.

  12. SiliaMetS® Diamine

    SiliaMetS® Diamine

    SiliaMetS® Diamine (Si-DIA) is a proven scavenger for metals and electrophiles. It scavenges acids, acid chlorides, anhydrides, aldehydes, isocyanates, and chloroformates as well as Pb, Ni, and Cd.

  13. SiliaMetS® Triamine

    SiliaMetS® Triamine

    SiliaMetS® Triamine (SiliaMetS WAX-3, Si-TRI) is effective for scavenging metals such as Pb, Co, Ru and Pd. Our screening studies have shown it to be the preferred scavenger for Pb. It can also be used as a scavenger for acid chlorides, isocyanates and other electrophiles.

  14. SiliaMetS® Imidazole

    SiliaMetS® Imidazole

    SiliaMetS® Imidazole (Si-IMI) is a versatile metal scavenger for a variety of metals including Cd, Co, Cu, Fe, Ni, Pd, and Rh under a wide range of conditions and the preferred metal scavenger for iron catalysts.

    SiliaMetS Imidazole can also be used as an amine base in systems that are generally sensitive to basic conditions compared to other SiliaMetS supported bases.

  15. SiliaMetS® TAAcOH

    SiliaMetS® TAAcOH

    SiliaMetS® TAAcOH (SiliaMetS Triaminetetraacetic Acid) is a silica bound metal scavenger for Pd(0), Ni(0) and Cu. It is the supported version of EDTA in its free form. It is an effective scavenger for metals in low or zero oxidation states, which includes many of the most synthetically useful catalysts such as tetrakis-(triphenylphosphine)palladium(0).

  16. SiliaMetS® TAAcONa

    SiliaMetS® TAAcONa

    SiliaMetS® TAAcONa or (or SiliaMetS Triaminetetraacetate, sodium salt) is a silica bound metal scavenger for Pd(II), Ni(II) and Cu. It is the supported version of EDTA in its sodium salt form. It is an effective scavenger for metals in higher oxidation state, 2+ or higher.

  17. SiliaMetS metal scavenger kit (K30730B). Includes the following products: Cysteine, DMT, Imidazole, Triamine, TAAcOH, TAAcONa, Thiol & Thiourea

    SiliaMetS® Metal Scavenger Kit (K30730B)

    This metal scavenger kit includes the following products: Cysteine - DMT - Imidazole - Triamine - TAAcOH - TAAcONa - Thiol - Thiourea
  18. SiliaSep™ Flash Cartridges Amine

    SiliaSep™ Flash Cartridges Amine

    Good alternative for normal phase purification of compounds with basic properties, which would normally have to be purified by reversed-phase.

    SiliaSep flash amine cartridges offer a superior alternative to the other cartridges available on the market.

  19. SiliaSep™ Flash Cartridges Triamine

    SiliaSep™ Flash Cartridges Triamine

    SiliaSep flash triamine cartridges offer a superior alternative to the other cartridges available on the market.

  20. SiliaSep™ Flash Cartridges Diamine

    SiliaSep™ Flash Cartridges Diamine

    SiliaSep flash diamine cartridges offer a superior alternative to the other cartridges available on the market.

  21. SiliaSep™ Flash Cartridges Thiol

    SiliaSep™ Flash Cartridges Thiol

    SiliaSep flash thiol cartridges offer a superior alternative to the other cartridges available on the market.

  22. SiliaSep™ Flash Cartridges TAAcOH

    SiliaSep™ Flash Cartridges TAAcOH

    SiliaSep flash TAAcOH cartridges offer a superior alternative to the other cartridges available on the market.

  23. SiliaSep™ Flash Cartridges TAAcONa

    SiliaSep™ Flash Cartridges TAAcONa

    SiliaSep flash TAAcONa cartridges offer a superior alternative to the other cartridges available on the market.

  24. SiliaSep™ Flash Cartridges Thiourea

    SiliaSep™ Flash Cartridges Thiourea

    SiliaSep flash thiourea cartridges offer a superior alternative to the other cartridges available on the market.

  25. SiliaSep™ Flash Cartridges Dimercaptotriazine (DMT)

    SiliaSep™ Flash Cartridges Dimercaptotriazine (DMT)

    SiliaSep flash DMT cartridges offer a superior alternative to the other cartridges available on the market.

  26. SiliaSep™ Flash Cartridges Cysteine

    SiliaSep™ Flash Cartridges Cysteine

    SiliaSep flash cysteine cartridges offer a superior alternative to the other cartridges available on the market .

  27. SiliaSep™ Flash Cartridges - Open Top (OT) Amine

    SiliaSep™ Flash Cartridges - Open Top (OT) Amine

    SiliaSep OT flash cartridges are compatible with FlashMaster instrument.

    Good alternative for normal phase purification of compounds with basic properties, which would normally have to be purified by reversed-phase.

  28. SiliaSep™ Flash Cartridges - Open Top (OT) Thiol

    SiliaSep™ Flash Cartridges - Open Top (OT) Thiol

    SiliaSep OT flash cartridges are compatible with FlashMaster instrument.

  29. SiliaSep™ Flash Cartridges - Biotage™ Compatible (BT) Amine

    SiliaSep™ Flash Cartridges - Biotage™ Compatible (BT) Amine

    SiliaSep BT flash cartridges are compatible with Biotage i-style compression modules.

    Good alternative for normal phase purification of compounds with basic properties, which would normally have to be purified by reversed-phase.

  30. SiliaPrep™ SPE Cartridges Amine (WAX)

    SiliaPrep™ SPE Cartridges Amine (WAX)

    SiliaPrep Amine is a weak anion exchanger sorbent used in replacement of SAX for strong anions to avoid irreversible retention. Can also be employed as a metal scavenger and in normal phase conditions.

  31. SiliaPrep™ SPE Cartridges Amine nec (WAX)

    SiliaPrep™ SPE Cartridges Amine nec (WAX)

    SiliaPrep Amine nec is a weak anion exchanger sorbent used in replacement of SAX for strong anions to avoid irreversible retention. Can also be employed as a metal scavenger and norman phase conditions.

  32. SiliaPrep™ SPE Cartridges Diamine

    SiliaPrep™ SPE Cartridges Diamine

    SiliaPrep Diamine can be used in replacement of SAX for strong anions. It can also be employed as metal scavenger and in normal phase conditions.

  33. SiliaPrep™ SPE Cartridges Diamine nec

    SiliaPrep™ SPE Cartridges Diamine nec

    SiliaPrep diamine can be used in replacement of SAX for strong anions to be irreversible retention. Can also be employed as metal scavenger and in normal-phase conditions.

  34. SiliaPrep™ SPE Cartridges Triamine

    SiliaPrep™ SPE Cartridges Triamine

    SiliaPrep Metal Scavengers will lower the residual metal concentration of various metal complexes to single digit ppm.

  35. SiliaPrep™ SPE Cartridges Thiol

    SiliaPrep™ SPE Cartridges Thiol

    SiliaPrep Metal Scavengers will lower the residual metal concentration of various metal complexes to single digit ppm.

  36. SiliaPrep™ SPE Cartridges Thiourea

    SiliaPrep™ SPE Cartridges Thiourea

    SiliaPrep Metal Scavengers will lower the residual metal concentration of various metal complexes to single digit ppm.

  37. SiliaPrep™ SPE Cartridges TAAcOH

    SiliaPrep™ SPE Cartridges TAAcOH

    SiliaPrep Metal Scavengers will lower the residual metal concentration of various metal complexes to single digit ppm.

  38. SiliaPrep™ SPE Cartridges TAAcONa

    SiliaPrep™ SPE Cartridges TAAcONa

    SiliaPrep Metal Scavengers will lower the residual metal concentration of variois metal complexes to single digit ppm.

  39. SiliaPrep™ SPE Cartridges Dimercaptotriazine (DMT)

    SiliaPrep™ SPE Cartridges Dimercaptotriazine (DMT)

    SiliaPrep Metal Scavengers will lower the residual metal concentration of various metal complexes to single digit ppm.

  40. SiliaPrep™ 96 Well Plates Amine

    SiliaPrep™ 96 Well Plates Amine


    Standard SiliaPrep 96 Well Plates are available in 2 mL with different bed weight up to 200 mg. Various sorbents are available and are divided into several sections based on sorbent characteristics.
  41. SiliaPrep™ 96 Well Plates Amine nec

    SiliaPrep™ 96 Well Plates Amine nec


    Standard SiliaPrep 96 Well Plates are available in 2 mL with different bed weight up to 200 mg. Various sorbents are available and are divided into several sections based on sorbent characteristics.

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