In the course of a recent project, a 11 step synthesis involved a late stage racemic intermediate, that required resolution into its enantiomers. The functional groups of the molecule did not allow for classical resolution and the development of an asymmetric synthesis was inconceivable within the given time frame. At that stage, as a result of not being able to recycle the undesired isomer, a 50 % loss of this late stage intermediate had a dramatic impact on the cost of goods for the product and the potential economic success of the program.

Through a joint development program with our customer, the synthesis was developed into a highly effective and efficient process. Simulated Moving Bed  (SMB ) chromatography was successfully employed for the resolution of the late stage intermediate, with the inclusion of a new process for recycling of the unwanted isomer through in-process racemization. This process resulted in an overall yield of 85 % of the desired enanatiomer in high optical purity from the racemate.

In less than one week, the process throughput was optimized to 1.4 kg of racemate per day. To date more than one metric ton of the intermediate has been produced using this process.