posted on 2021-07-16, 18:11authored byChristopher
G. Thomson, Colin Banks, Mark Allen, Graeme Barker, Christopher R. Coxon, Ai-Lan Lee, Filipe Vilela
Recent advancements in in-line extraction
and purification technology
have enabled complex multistep synthesis in continuous flow reactor
systems. However, for the large scope of chemical reactions that yield
mixtures of products or residual starting materials, off-line purification
is still required to isolate the desired compound. We present the
in-line integration of a commercial automated flash chromatography
system with a flow reactor for the continuous synthesis and isolation
of product(s). A proof-of-principle study was performed to validate
the system and test the durability of the column cartridges, performing
an automated sequence of 100 runs over 2 days. Three diverse reaction
systems that highlight the advantages of flow synthesis were successfully
applied with in-line normal- or reversed-phase flash chromatography,
continuously isolating products with 97–99% purity. Productivity
of up to 9.9 mmol/h was achieved, isolating gram quantities of pure
product from a feed of crude reaction mixture. Herein, we describe
the development and optimization of the systems and suggest guidelines
for selecting reactions well suited to in-line flash chromatography.