Solid-Supported Scavengers

A wide range of chemistries employed within the pharmaceutical industry use metal-based catalysts however, with regulations becoming increasingly stringent with respect to the quantities of trace metals tolerated within final products, novel techniques are finding application in such reactions. 

Although the field of micro reaction technology has provided overwhelming evidence to show that reactions are more efficient and products can be synthesized in higher purity compared with conventional batch procedures, trace metal contamination of the resulting compounds can still present a problem. 

Coupled with the fact that the proportion of trace metal contaminants detected within continuous flow reaction products is inherently low, due to reduced catalyst degradation, the use of a scavenger cartridge at the end of a reaction sequence represents a relatively long-term solution to this problem. Other examples of the use of solid-supported scavengers have been reported by Ley and co-workers [65], where in one example, two scavenger modules, comprising QuadraPure TU (126) and phosphane resin, were used in the synthesis of 1,4-disubstituted-l,2,3-triazoles [66], and by Watts and co-workers [67], where silica-supported copper sulfate was used for the removal of residual dithiol (ppb) in the synthesis of 1,3-dithiolanes and 1,3-dithianes. 

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Incorporation of Solid-supported Scavengers into Library Synthesis... 

Kaldor [49 i, 55] demonstrated the advantages of applying solid-supported scavengers to the preparation of parallel arrays in a multi-step fashion. In these studies he examined the clean-up of multiple amine alkylation and acylation reactions using a variety of immobilized electrophilic and nucleophilic scavenger reagents including an amine, isocyanate, aldehyde and acid chloride (Tab. 2.1). 

This strategy has previously been referred to as t A nucleophilic polymer is a scavenger of solid-supported scavengers (SSS), polymer- electrophiles and vice versa,... 

Figure 8.32 Solid-supported scavengers basic principles.

Figure 8.33 Solid-supported scavengers tagging reagents 8.54-8.57 and supported, covalent...

Figure 8.34 Solid-supported scavengers purification of the P-amino alcohol 8.64 using the covalent scavenger 8.62.

Figure 8.35 Solid-supported scavengers sequestration-enabling reagents 8.65-8.70.

The concept of selective sequestration of non-product species was first demonstrated using solid-supported scavengers with electrophilic and nucleophilic character in amine acylation, amine alkylation, and reductive amination protocols [46]. Since then, a wide range of scavenger reagents has become commercially available from various suppliers. The structures and functions of these scavenger resins are shown in Table 1. 

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