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Efficient Ruthenium Scavenging Using SiliaMetS
Achieved by Genentech Inc, a Member of the Roche Group

Efficient Ruthenium Scavenging Using SiliaMetS

This work describes a scalable catalytic asymmetric hydrogenation process for the multikilogram-scale production of a β2-amino acid.

The efficient synthesis of chiral β2-amino acid derivatives, which are key components of medicinally active compounds, is well-achieved, but their kilogram-scale production remains a challenge. Herein, a short and efficient synthesis of the starting unsaturated N-Boc-protected β2-enamide was developed. Furthermore, an extensive catalysis screening and optimization study identified a simple Ru-BINAP catalyst (a [BINAP-RuCl(benzene)]Cl complex) to directly afford the (S) product in high enantiomeric excess and yield.

The final process enabled a multikilogram production in >99% ee, to be used as a key component for one of their clinical candidates.
Upon Scale-Up studies for the synthesis of the β2-Amino Acid, it was found that upon increasing scale, similar catalyst loading could achieve similar full conversion.

The combined batches of crude product were treated with SiliCycle SiliaMetS Thiol R51030B to scavenge the residual Ruthenium. Crude product was then crystallized from heptane to produce a total of 126 kg of the β2-Amino Acid in ˃99.9% ee and ˃ 99A% purity by HPLC.

Remarchuk, T., et al.; Organic Process Research & Development, 2014, 18, 135-141.

 

SiliaMetS Metal Scavengers


SiliaMetS Metal Scavengers are functionalized silica gels designed to react and bind excess metal complexes.

Silica-based metal scavengers have been proven to be the purification method of choice over all other methods and several companies from various industries use them.
With the silica matrix advantages over polymers (no swelling, more general solvent compatibility, higher mechanical and thermal stabilities, applications easily scalables and products available in different formats (SPE, flash cartridges and bulk), etc.) combined to SiliCycle’ expertise in grafting technology, SiliaMetS are the solution for metal removal without contamination of drug candidates
SiliaMetS are highly selective and offer a cost-effective alternative for metal scavenging.

SiliaMetS Thiol

SiliCycle Metal Scavenger - SiliaMetS Thiol

SiliaMetS Thiol (Si-Thiol) is a robust metal scavenger for a variety of metals including Pd, Pt, Cu, Ag and Pb under a wide range of conditions. It has been used in pharmaceutical processes up to the pilot plant scale. It is our most versatile metal scavenger and is the preferred metal scavenger for Pd(II), Cu, Ag, and Hg.

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