The development of a pilot-scale synthesis of the rufinamide precursor in flow chemistry is reported. Complex steps such as Taylor-flow, segmented flow, and high-temperature processing at high pressure (high-p,T) are successfully combined, overcoming the mixing and heat transfer issues of the scale-up. The cascaded multistep process operates essentially solvent-free in just 3 m2 giving a productivity of 47 g/h (>400 kg/year), which increases by a factor of 7 the lab-scale productivity previously reported as a scale-up proof-of-concept. This publication also includes an economic study of the feasible implementation of this technology for a possible manufacturer, as well as an outline on business development strategies of how to implement such a disruptive technology.

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In the pharma and fine chemical industries, the development of continuous flow technologies is a process intensification step of primary importance towards the manufacturing of high-quality products, while reducing the environmental impact and cost of production. The sustainability and profitability of a process can be measured through life cycle Assessment and cost evaluation. However, when applied to emerging technologies, these need to be performed at different stages of the process development in order to limit the uncertainties arising from the scale-up, and hence providing high-fidelity projections of environmental impacts and costs at larger scales. The output of the assessment can in fact vary significantly depending on the maturity of the technology and this translates into having different results at commercial scale compared to early estimations. Therefore, in this article, we perform an assessment at two different scales of production, lab and mini-pilot scale, with the aim of quantifying the uncertainties of the assessment related to the scale-up, identifying the hotspots of the system, and hence providing guidelines for the further steps of process development. The subject of the assessment is the continuous flow synthesis of Rufinamide. It is the first time that this synthesis is evaluated at pilot-scale. The results show that low yields in the cycloaddition drastically affect the waste management and the production of precursors, and hence increases environmental impacts and cost of production. This calls for the need of prioritizing the optimization of this synthesis step in order to deploy a green and economically competitive production technology.

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