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

Green Processing and Synthesis

article

Leo Leroyer¹  Laurent Prat¹  Michel Cabassud¹  Christophe Gourdon¹  Odile Dechy-Cabaret²  Matthieu Barthes⁴  Philippe Camus⁴  Stephane Hattou⁴ 

[1] Laboratoire de G é nie Chimique (LGC);Laboratoire de Chimie de Coordination (LCC);Universit é de Toulouse;SANOFI-AVENTIS

关键词: fast process development;    intensification;    microreactor;    pharmaceuticals;    reaction engineering;   

DOI  :  10.1515/gps-2013-0026

来源: De Gruyter

【 摘 要 】

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.

【 授权许可】

CC BY