The implications of the use of surfactant TPGS-750-M in water as a micellar reaction medium on the concomitant aqueous waste streams and their sustainable disposal have been studied. Biodegradability, log P ow, solubility, and German water hazard class of the surfactant have been determined and enabled establishment of a waste water concept, which builds on the lipophilicity and ester group lability of the molecule. The presented data and examples suggest preferred ways for designing surfactant processes and their aqueous waste streams in a sustainable manner.

A novel and concise synthesis of the DP2 receptor antagonist Fevipiprant (NVP-QAW039) was developed. The initial research route was suffering from a long reaction sequence to the functionalized 7-aza-indole core followed by a poorly selective N(1)-alkylation with the benzyl side chain. These limitations were overcome by introducing the side chain early by reductive amination between the functionalized aldehyde and 2-amino-3bromopyridine. The Sonogashira coupling with prop-2-yn-1-ol introduces the 3 missing carbon atoms to build the 7-aza-indole core and sets the stage for the innovative Johnson-Claisen key step. The reaction of the advanced propargylic alcohol derivative with trimethyl orthoacetate led to a reactive allene intermediate which spontaneously and selectively cyclizes to the 7-aza-indole QAW039-methyl ester. QAW039 was isolated after ester saponification. Selectivity, yield, and ecological footprint of the new synthesis were significantly improved, and scalability was demonstrated.