Researchers from the Department of Chemistry at the University of Cambridge in the UK claim to have made a potential breakthrough in the manufacture of breast cancer drug Tamoxifen using flow chemistry developed by specialist chemical engineering firm Vapourtec.
A paper published in the journal Organic Process Research and Development, called Continuous flow-processing of organometallic reagents using an advanced peristaltic pumping system and the telescoped flow synthesis of (E/Z)-tamoxifen, describes the use of Vapourtec’s E-Series flow chemistry system, which enables organometallic reagents to be processed.
The telescoped continuous flow process described in the article produces Tamoxifen at the rate of one dose every five seconds.
The newly developed Vapourtec V-3 pump, a chemically resistant peristaltic pumping system, is at the heart of a process which allows chemists continually to pump highly reactive substances, which can permit the use of reactive intermediates. The use of such reactive chemicals were then harnessed to prepare Tamoxifen.
Existing approaches for pumping organometallic reagents, such as n-butyllithium, Grignard reagents and DIBAL-H, can present a number of challenges due to sensitivity to air and moisture, however, Vapourtec says the V-3 pump eliminates these issues.
The simplified pumping of organometallic species have allowed us to access reactions and reactivity that we have previously found difficult
Based on the peristaltic principle, the V-3 can deliver a smooth flow at up to 10 bar pressure and even self prime from pipes that are full of air.
The wetted area inside the V-3 pump is small and can be easily and rapidly dried using an anhydrous solvent. Reagents can be fed directly from a bottle sealed with a septum which eliminates the need to manually handle potential pyrophoric reagents.
The V-3 does not feature check valves or sliding seals, which means that the occasional generation of suspended particles of insoluble salts, caused by small amounts of moisture, presents no problem to the process.
Duncan Browne, a flow chemist involved in the research project, said: 'The V-3 pump has enabled us to expand previous flow chemical reactions into truly continuous processes that produce significant quantities of materials. The simplified pumping of organometallic species have allowed us to access reactions and reactivity that we have previously found difficult.'
Andrew Mansfield, Applications Specialist at Vapourtec, added: 'This is a perfect example of how technological innovation in the field of flow chemistry can deliver more effective and efficiently manufactured solutions for a wide variety of industries, including pharmaceuticals.'