217448-86-7Relevant articles and documents
Organic synthesis in a modular robotic system driven by a chemical programming language
Steiner, Sebastian,Wolf, Jakob,Glatzel, Stefan,Andreou, Anna,Granda, Jaros?aw M.,Keenan, Graham,Hinkley, Trevor,Aragon-Camarasa, Gerardo,Kitson, Philip J.,Angelone, Davide,Cronin, Leroy
, (2018/12/14)
The synthesis of complex organic compounds is largely a manual process that is often incompletely documented. To address these shortcomings, we developed an abstraction that maps commonly reported methodological instructions into discrete steps amenable to automation. These unit operations were implemented in a modular robotic platform by using a chemical programming language that formalizes and controls the assembly of the molecules. We validated the concept by directing the automated system to synthesize three pharmaceutical compounds, diphenhydramine hydrochloride, rufinamide, and sildenafil, without any human intervention. Yields and purities of products and intermediates were comparable to or better than those achieved manually. The syntheses are captured as digital code that can be published, versioned, and transferred flexibly between platforms with no modification, thereby greatly enhancing reproducibility and reliable access to complex molecules.
From alcohol to 1,2,3-triazole: Via a multi-step continuous-flow synthesis of a rufinamide precursor
Borukhova, Svetlana,No?l, Timothy,Metten, Bert,De Vos, Eric,Hessel, Volker
, p. 4947 - 4953 (2016/10/06)
Rufinamide is an antiepileptic drug used to treat the Lennox-Gastaut syndrome. It comprises a relatively simple molecular structure. Rufinamide can be synthesized from an organohalide in three steps. Recently we have shown that microreactor flow networks have better sustainability profiles in terms of life-cycle assessment than the respective consecutive processing in a batch. The analysis was based on the results of a single step conversion from batch to continuous mode. An uninterrupted continuous process towards rufinamide was developed, starting from an alcohol precursor, which is converted to the corresponding chloride with hydrogen chloride gas. The chloride is then converted to the corresponding organoazide that yields the rufinamide precursor via cycloaddition to the greenest and cheapest dipolarophile available on the market. The current process demonstrates chemical and process-design intensification aspects encompassed by novel process windows. Single reaction steps are chemically intensified via a wide range of conditions available in a microreactor environment. Meanwhile, the connection of reaction steps and separations results in process-design intensification. With two in-line separations the process consists of five stages resulting in a total yield of 82% and productivity of 9 g h-1 (11.5 mol h-1 L-1). The process minimizes the isolation and handling of strong alkylating or energetic intermediates, while minimizing water and organic solvent consumption.
Pressure-accelerated azide-alkyne cycloaddition: Micro capillary versus autoclave reactor performance
Borukhova, Svetlana,Seeger, Andreas D.,Nol, Timothy,Wang, Qi,Busch, Markus,Hessel, Volker
, p. 504 - 512 (2015/03/04)
Pressure effects on regioselectivity and yield of cycloaddition reactions have been shown to exist. Nevertheless, high pressure synthetic applications with subsequent benefits in the production of natural products are limited by the general availability o
