Lehmann, Hansjoerg (2018) Diazomethane and Flow Chemistry: Filling a Gap in Pharma R&D. Chimica oggi : = Chemistry today..

Abstract

A scale-up of hazardous reactions in batch requires extensive safety investigations which can cause massive delays for the scale-up process of pharmaceutical intermediates and active molecules. Continuous flow chemistry as an enabling technology nowadays has proven that it can help to reduce the safety hazards thus bringing back neglected chemistries into synthesis laboratories where in the past quite often the application of those reactions was avoided. One of those hazardous but very useful reagents is diazomethane which is a valuable C1-building block for organic synthesis. A safe handling of diazomethane on larger scale in a batch reactor is almost impossible but the hazards of preparing and reacting diazomethane however can be minimized significantly under continuous flow conditions. Recently, we developed a simple and robust continuous flow process for a safe on-demand generation of diazomethane and its precursor N-methyl-N-nitrosourea (MNU). The developed two-step process starts from non-hazardous N-methylurea, generates and consumes N-methyl-N-nitrosourea (MNU) and diazomethane in-line and enables a safe and convenient scale-up to multi-gram scale in a conventional synthesis laboratory.

Item Type:	Article
Keywords:	continuous flow chemistry; hazardous reactions; scale-up; diazomethane
Date Deposited:	22 Sep 2018 00:45
Last Modified:	22 Sep 2018 00:45
URI:	https://oak.novartis.com/id/eprint/36045