Innovation in Route Design, (Bio)Catalysis and Process Development Applied to the Second Generation Synthesis of Sacubitril

Commercial manufacturing processes in the pharmaceutical industry need to address numerous goals, ranging from cost effectiveness over process safety to environmental sustainability. While the design of the synthetic route may commonly be considered the centerpiece of chemical process development, only the combination with innovative technologies at scale and in-depth process understanding can unlock the full potential of a synthetic route. The development of a second-generation synthesis of sacubitril, one of the constituent active pharmaceutical ingredients of LCZ696, serves as an example to display how synthesis design can be successfully combined with (bio)catalysis and thorough process development to achieve superior results. In addition, the case at hand highlights the multidisciplinary and team-focused nature of chemical process development.