When Scaling Up a Synthetic Organic Intermediate that is being Purified by Distillation

If an intermediate is being worked up, isolated, and purified by distillation as part of developing a chemical process for synthesis at scale that should trigger consideration in its synthesis for using a high boiling solvent which can act as a chaser during the contemplated large-scale distilling.

The volume of this ‘chaser’ phase should be sufficient to completely occupy the ‘minimal storable volume’ in the reactor contemplated in the eventual scale-up.

This will almost always involve replacing a traditional lower boiling solvent as part of the modifications of a literature model example. These chaser phases must almost always be acceptable in cost to the solvents they replace. Because product is lost whenever it is essentially the highest boiling part of the reaction mixture because some material must always remain boiling in the still pot even at the end of the fractionation, using an appropriate chaser will save money that will be partially lost from whatever extra cost is involved in using the chaser.