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A two reaction synthesis of a urea, using triphosgene, was studied. The objective was to transpose the process from laboratory scale to pre-industrial plant. The whole study was performed in a continuous process, adapting the characteristic dimensions and length of the reactor. In this paper, the development of the process is presented, and the choices about safety and operating conditions constraints are discussed. The final operation allows a 70% global yield in a 7 week study. Furthermore, the use of microreactors not only permits an exhaustive study of the process operating parameters, but also provides feedback on the developed chemistry itself. The results obtained are a demonstration of the use of continuous processes in small scale reactors for complex molecule development. The mg·h -1  to kg·h -1  is a key transposition in the pharmaceutical industries project development, as it can help to accelerate the first lot production used in toxicological or pre-clinic stages.

Transposition of a triphosgene-based process for pharmaceutical development: from mg·h -1 to kg·h -1 of an unsymmetrical urea