How to process 200g of racemate within a working week

Eight years ago, when Reach was starting out, the idea of purifying 200g of racemate would have been terrifying.

Reach began with the aim of supporting discovery chemistry, something that we did so well our reputation quickly grew. Not only did we have to scale out to accommodate our growing client base. We also had to scale up to help support our clients into early development.

Time and again we have seen <100mg separations scale up to one gram, tens of grams and hundreds of grams. With clients choosing the fail fast approach, continuing with chromatography into development, rather than taking the often time-consuming and ultimately expensive, synthetic approach.

SFC pumps capable of running large schal chiral separations.
Pumps capable of pumping supercritical carbon dioxide up to 180g/minute.

Large scale chiral separations (200g and up) are now common place within the Reach laboratory. In the last six months we have seen three projects of 500g and greater. All of which have been delivered to strict deadlines.

Firstly, we had to go bigger.

Using columns of 30mm diameter, rather than 20mm, more than doubles the amount of material that can be loaded on to the column at once. However, in order to get the full benefit from a 30mm column we needed a system that could power them optimally. That is where our ABsys came in. Two years ago, we opted to customise a Gilson HPLC kit and turn it into a preparative SFC. Now capable of flow rates over 180g/minute, with automated cylinder switching and a carbon dioxide booster pump, this kit can comfortably run unattended for hours into the night, often processing up to five grams of racemate an hour.

Higher flow rates and increased running hours meant that the bottleneck was moved from purification to post processing. To stop this becoming an issue we looked at our evaporation capacity and made some changes. Without the luxury of walk in fume cupboards, larger rotary evaporators were not an option. Instead, we had to find a way to make our two-litre rotary evaporators work harder. With the addition of two syringe pumps and  custom coding to monitor the pressure of the diaphragm pump, these evaporators can be autofilled and emptied throughout the day and into the night.

All these changes mean that we no longer have a bottle neck in the process. Which allows us to process large scale separations both efficiently and economically.

You can find out more about our chiral capabilities across all scales, here: