A Chemistry in Water Reproducibility Study: Learnings from a Pre-Competitive, Multi-Company Collaboration

Despite the reported successes and advantages involving the use of amphiphilic surfactants, most notably TPGS-750-M, to enable a multitude of synthetic transformations to be conducted in water, implementation of this methodology within the pharmaceutical industry has been relatively limited. In this paper, we will disclose the key results and learnings from a multi-company collaboration focused on a reproducibility study involving some of the most commonly used reaction types in the pharmaceutical industry, specifically amidation, SNAr, nitro reduction, reductive amination and multiple Pd-catalyzed transformations in water. Key to this study will be the presentation of results not just from the originally reported TPGS-750-M conditions, but also under the water-only control and with three different surfactants, as well as on both small (i.e., <500 mg) and mid (~10 g) scales.