Multicolumn Chromatography-Development of Route

With a supply route estabhshed (route 2) and supplies of radafaxine available to fund the initial development activities, focus switched to discovering a more efficient synthesis. Environmental considerations were a key consideration, and a dual program of work was initiated to address these concerns. One approach was to investigate the feasibihty of identifying a Dynamic Resolution to avoid the losses associated with the undesired (R,R)-enantiomer, discussed above, while, in parallel, the viability of employing continuous chromatography to separate the enantiomers was examined. 

Based on information available in the public domain, about twelve commercial MCC systems with column diameters ranging from 20 to 100cm have been installed worldwide since 1997. In 2005 it was estimated that the largest units used in the pharmaceutical industry were processing up to 200 tonnes of material 

Schematic provided and reproduced with the permission of Oiivier Dapremont (Ampac Fine Chemicais LLC) 

Although MCC is a chromatographically based technique, the process is generally considered to be environmentally friendly, as high production rates are possible, solvent loss is minimal (it is recovered during product isolation and recycled back into the system), and the silica-based stationary phase is reported to last at least 3-4 years. 

It was envisaged that MCC would address several of the issues associated with the chemistry, for example  

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