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Sale of Biotage's facility in Charlottesville, Virginia
Biotage moves to 100% direct sales for SPE products in the UK
Interim report January-September 2009

Unique Evaporation Technology Proves to be a Breakthrough Concept and Effective Time Saver for Big Pharma Biotage Partners with John Morris Scientific for Distribution in Australia and New Zealand

PittConBooth #750
Orlando, FL
March 1-4
11th LABORTECHNIKA EXHIBITIONBudapest, Hungary
March 16th - 19th

ACSSan Francisco, CA
March 21-24

Analytica 2010Munich, Germany
March 23rd-26th

2nd Int Chester Food Science & Technology meeting (ICFST)Chester University, United Kingdom
March 22nd - 24th

5th National Meeting on Environmental Mass SpectrometryChester University, United Kingdom
March 24th

 

Quickly and Easily Remove Residual Metals
from APIs to Approved Levels

Biotage is now able to offer multi-kilogram quantities of
ISOLUTE® Si-Thiol, MP-TMT and NEW ISOLUTE Si-TMT for
your metal scavenging needs.

Solid supported metal scavengers have been shown to offer a highly selective,
cost-effective scavenging process for reaching purity goals.

Precious group metal (PGM) catalyzed reactions are commonly used in the manufacture of active pharmaceutical ingredients (APIs) and fine chemicals. The tolerated limits for metal content are becoming increasingly more challenging, for example, the USA and EU FDA require concentration levels for many metal ions to be less than 5ppm for candidate drug progression.

Traditional methods used to remove metals include chromatography, activated carbon, extraction, distillation and recrystallization but, these offer poor selectivity and can lead to high API loss.

ISOLUTE® Si-Thiol
ISOLUTE Si-Thiol is the silica-bonded equivalent of 1-propanethiol, which is useful for covalent scavenging of electrophiles. The main application is the use to scavenge a variety of metals1,2 used in organic chemistry including Pd, Pt, Cu, Hg, Ag and Pb,
Figure 1.

More recently, these types of materials have also been investigated in the removal of colored impurities from APIs.3

Fig 2 Kg Resins
Figure 1. Chart showing scavenging trends from 3M solution of Dichlorobis(TPP)Palladium II (3 mL) in 1:1 DMF:THF over 16h.

ISOLUTE® Si-TMT

ISOLUTE SI-TMT is the silica bound equivalent of 2,4,6-trimercaptotriazine (TMT). Si-TMT has been shown to efficiently scavenge residual palladium from palladium-catalyzed reactions. More recently, these types of materials have also been investigated in the removal of colored impurities from APIs.3

SI-TMT Chart and Part numbers KG RESIN_Stability Profile.jpg

MP-TMT (>0.5 mmol/g)

MP-TMT is a macroporous polystyrene-bound trimercaptotriazine, a resin bound equivalent of 2,4,6-trimercaptotriazine (TMT). MP-TMT scavenges residual palladium from palladium-catalyzed reactions and has also shown to remove other metals. The MP-base copolymer has been redesigned to yield a more robust, low swelling material, which makes it ideal for restricted volume environments. Its unique pore structure provides greater access to the reactive sites resulting in faster reactions and higher recoveries.


Fig 1 Kg Resins
Figure 1. MP-TMT or competitor TMT resin was stirred with Pd(Cl)2(PPh3)2 in THF/DMF (50:50) (2mL / total 8 µmole / 852ppm Pd) for 16 hours at RT, and residual Pd determined following this scavenging.

Examples of applications
Examples of Applications



Industrial application

Selective Removal of Palladium from Process Stream after workup of a Suzuki-Miyaura
coupling reaction (Adsorbent screening conducted at 50 wt % loading)2. MP-TMT has shown to be the most efficient palladium scavenger.

Industrial application

Apparent
 

Ordering Information

SI-TMT Chart and Part numbers KG Resins_Part Numbers.jpg

References
1 Crudden, C.M.; Sateesh, M; Lewis, R.; J. Am. Chem. Soc. 2005, 127 (28), 10045-10050.
2 Welsh, C.J.; Albaneze-Walker, J.; Leonard, W.R.; Biba, M.; Da Silva, J.; Henderson, D.; Laing, B.; Mathre, D.J.; Spencer, S.; Bu, X.; Wang, T. Org. Process Res. Dev. 2005, 9, 198-205.
3 Welch, C.J; Leonard, W.R.; Henderson, D.W.; Dorner, B.; Glaser Childers, K.; Chung, J.Y.L.; Hartner, F.W.; Albaneze-Walker, J.; Sajonz, P. Org. Process Res. Dev. 2008, 12, 81-87.
4 S. Rana, Unpublished Results, Biotage 2008. Method as per: Heo, Y.; Song, Y.S.; Kim, B.T.; Heo, J. Tetrahedron Lett., 2006, 47, 3091-3094. 


 

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