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and the relatively low cost for the reactive parts in the set-up, dedicated or single-use coils and reactors can be used, eliminating contamination hazards.
Finally, multi-stage continuous processes can circumvent the need to store synthetic intermediates, avoiding degradation and other stability issues. The net working capital required for multi-stage continuous processes is also lower than for batch processes.
Focus on sustainable manufacturing
Continuous processing is a key technology for green chemistry. The superior mixing and heat transfer enables chemical reactions to be carried out in more concentrated ways or even without solvent, minimising waste. 3 Continuous flow processes often show greater productivity and can further decrease solvent consumption by applying in-line extraction techniques that typically operate with less solvent.
A paradigm shift
In a recent webinar,‘ The Paradigm Shift to Continuous Flow Processes: A Holistic View’, Dr Bert Metten( pictured), technology development manager at Ajinomoto, explored Ajinomoto Bio-Pharma’ s proven expertise and capabilities in handling dangerous chemistries.
Recently, the team was able to demonstrate its experience with challenging chemistries related to scale-up using diazomethane, an extremely sensitive and volatile chemical that is used in producing the precursor for a client’ s cyclopropanated product.
The primary challenge— establishing a sustainable, economically competitive manufacturing process for the product— made this an ideal candidate for translation from batch to flow. While the chemical steps to the diazomethane precursor were relatively simple on paper, there were a few inherent issues with optimising the process with continuous flow.
The project, which began in 2014, involved a three-step process: two based on an existing diazomethane procedure and the third for in situ diazomethane generation and cyclopropanation. It was highly complex for many reasons related to the hazards of the chemistry, analytics, waste streams and reactor vessels, among others. Finally, scale-up to production( 28x pilot scale) in a dedicated set-up was realised in 2020. Ultimately, Ajinomoto was able to demonstrate that transitioning to continuous flow afforded a far more selective reaction. This enabled the team to push reaction conditions in order to achieve optimal results, reducing diazomethane precursor consumption by 20 %, precious metal catalyst usage by 25 %, and base and solvent amounts by 50 %. Based on the latest results from the customer’ s commercial plant, we were able to improve the cost of goods, reducing costs by 10-25 % and waste treatment costs by 46 %.
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