Abstract

Continuous Flow Development – From Library Synthesis to Solid-Phase Chemistry

Manuel Nuño, Research Scientist, Vapourtec Ltd.

The first part of this presentation will cover different approaches to perform catalysis in flow, depending on the type of catalyst, reagents and the source of energy used. Manuel will show examples of high selectivity homogeneous decarboxylative cross coupling libraries, difficult to reproduce in batch; scale up of photochemical processes from 370 g/day to 1.4kg/day. Continuous flow solid-phase peptide synthesis (CF-SPPS) offers the possibility to work at high temperature, minimising cycle time, reducing the consumption of solvents and reagents and benefiting from inline data. By using data analytics from UV/Vis detector and measuring the reactor volume change, events such as aggregation in the sequence can be quickly evaluated and corrections made. Aggregation on GLP-1, JR-10 and ACP peptides have been assessed and different chemical solutions implemented to yield the final peptide with high purity. Suspended solids in flow is typically synonym to reactor blockage but depending on the physical properties of the solid reagent, they can be handled as slurry in tubular reactors. Pd on charcoal is an excellent catalyst for hydrogenations, but due to its small particle size, it can be challenging to pack in a column without causing blockages. By pumping slurries of it up to 100 mg/ml, a 6 g/h throughput of an API intermediate was achieved in a 3-phase hydrogenation reaction.