Reaction miniaturization in eco-friendly solvents

Advanced chemical intermediates used in pharmaceutical research are often produced for the first time via multistep synthetic routes that are neither optimal nor green. For this reason, every milligram of an advanced chemical intermediate is precious and should be conserved as much as possible in exploratory studies. This Review describes the role that the emerging field of reaction miniaturization can play in the ultra-conservation of advanced pharmaceutical intermediates and additionally in the overall reduction of waste achieved by performing reactions on a smaller scale. We highlight technologies, with case studies, for running synthetic reactions in parallel from the milligram to microgram scale in glass vials and plastic wellplates. A unique synergy of reaction miniaturization and green chemistry is revealed in their shared preference for high-boiling reaction solvents.