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By Evan Riley, Communication Associate, ACS Green Chemistry Institute
Established in 2016 by the ACS GCI Pharmaceutical Roundtable, the Peter J. Dunn Award recognizes excellence in the research, development and execution of green chemistry that demonstrates improvements in environmental, safety and efficiency over current technologies in the pharmaceutical industry and its allied industrial partners. The award was established in honor of Peter J. Dunn of Pfizer.
Bailey’s technology, titled “Beyond Organic Solvents: Synthesis of a 5-HT Receptor Agonist in Water”, uses Takeda’s pre-existing TAK-954 process as a test case to demonstrate the feasibility of implementing reactions in water. The technology simultaneously comprises all three focus areas of the award, 1) greener more sustainable synthetic routes and their associated processes to Active Pharmaceutical Ingredients (API) or intermediates, 2) reaction conditions, and 3) chemical or manufacturing process technologies as applied at meaningful scale. Bailey’s technology achieves this by developing greener reaction conditions while reducing a six-step synthesis (all reactions and isolations from water) to four.
Bailey developed a potential alternative to Takeda’s TAK-954 six-step current manufacturing sequence to be run almost entirely in water. Doing this replaces five separate organic solvents and simultaneously implements five direct isolations from aqueous media. Key transformations carried out in aqueous media include a benzimidazole cyclization, amidation, reductive amination, and a selective oxidation of an aliphatic alcohol. Because the reductive amination and aliphatic alcohol oxidation using the new surfactant technology were not previously described in the literature, new methodologies were invented specifically for this application. In addition to shortening the synthetic route by two steps and removing the vast majority of organic solvents from the process, Bailey and his team were able to reduce the overall PMI (Process Mass Intensity) from 350 to 111. The team noticed that shifting the reaction and isolation media from organic solvents to water had additional benefits. These include reducing the portion of the PMI attributable to solvents from 223 to 19, and surprisingly, reducing the portion of the PMI attributable to water from 106 to 76.
Along with receiving the Peter J. Dunn Award for Green Chemistry & Engineering Impact in the Pharmaceutical Industry, Dan Bailey will be presenting his technology at the 2020 Green Chemistry & Engineering Conference. Nominations for the 2021 award will open in the fall. To find out more, visit: https://www.acsgcipr.org/educating-leaders/#awards