Abstract
The synthesis of drug substances (DS) requires the continuous effort of the pharma industry to ensure high sustainability standards. The Suzuki-Miyaura cross coupling is a fundamental C-C bond-forming reaction to produce complex DS intermediates. The present contribution points out the way in which the synthesis of DS intermediates by C-C cross coupling can be economically competitive, while minimizing waste by selecting the appropriate heterogeneous catalyst. By comparing homogeneous, immobilized heterogeneous catalysts on silica and metal-organic framework (MOF) catalysts, while considering the perspectives of academia and industry, the critical parameters for a successful industrial application of heterogeneous catalytic Suzuki-Miyaura cross coupling reactions were identified. Heterogeneous catalysts, such as MOFs, may provide a complementary platform for reducing waste and the costs of production related to such transformations.
Highlights
The chemical community must be on the lookout for new, innovative technologies that potentially reduce the costs of drug substance (DS) manufacturing processes due to the increasing pressure on the pharmaceutical industry to provide affordable drugs and cost-efficient therapeutic modalities for innovative healthcare
The phosphine metal–organic framework (MOF) (P-MOF) LSK-15 with MIL-101 topology[46] was tested as a solid ligand for the palladium-catalyzed coupling of bromoanisole with boronic acid, which enabled the determination of the C–C coupling and hydrodehalogenation selectivities.[47]
The heterogenization of homogeneous catalysts may become a powerful strategy for the industrial production of drug substances
Summary
The chemical community must be on the lookout for new, innovative technologies that potentially reduce the costs of drug substance (DS) manufacturing processes due to the increasing pressure on the pharmaceutical industry to provide affordable drugs and cost-efficient therapeutic modalities for innovative healthcare. The aim of Roche and the Paul Scherrer Institute collaboration on metal–organic frameworks (MOFs), highly crystalline and porous materials based on molecular building blocks, is to implement these catalytic materials in Suzuki-Miyaura cross coupling reactions to better understand their a) real-life performance, b) substrate tolerance, c) robustness, and d) ease of separation from the process-step product and to determine whether the MOFs result in more sustainable and cost-efficient processes than state-of-the-art, well-defined homogeneous palladium catalysts. Multi-purpose equipment is used in the production of a DS, GMP standards must be met, and the cleaning of the corresponding equipment is highly regulated to avoid cross-contamination by impurities (e.g., residual trace metals, organic and inorganic impurities, and potentially genotoxic compounds).[12] Metal leaching of the heterogeneous catalysts and reactor cleaning procedures need to be adequately addressed during process development to decide whether a new catalyst and process can be implemented or not. It is essential that all steps in the process are safe and that special measures are taken to ensure this
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
