Continuous multistep organolithium transformation
Reaction: Deprotonation of propionate, followed by its reaction with an electrophilic aldehyde and a subsequent quench to afford the aldol product
The Modular MicroReaction System (MMRS), is a globally unique piece of equipment for research and development work from Ehrfeld Mikrotechnik. With this system we provide users with a multiplicity of options for developing new processes and intensifying their existing ones. The modular design is the heart of the MMRS. Mounted on a base plate in the sizes A5 to A3, the micro- and milli-structured mixers, reactors and heat exchangers can be combined with maximized flexibility for an individually customized configuration. The MMRS offers optimum preconditions for imaging a multi-stage synthesis reaction in a minimized timeframe, and for performing this automatically. Thanks to automation capabilities like the LabManager®, developed specifically for laboratory applications, or by using your own solution, you will swiftly obtain a large amount of data on all process parameters – an important advantage in research and development work. The MMRS always gives you the degree of flexibility you need for feasibility studies and small-scale syntheses. Our MMRS modules have proved especially efficacious in sophisticated reactions like severely exothermic ones or when using toxic and potentially explosive substances. Further pluses include the sturdy construction and simple cleaning since almost all modules can be dismantled. With this intelligent laboratory toolkit, we offer research institutions and companies an entry into continuous reaction technology, with expandable scenarios: from MMRS, there is a seamless progression into the pilot and production scales: our spectrum includes the add-on reactor groupings Miprowa®, FlowPlate® and ART®, plus numerous special models.
FlowPlate® MicroReactors are the innovative solution for small and frequently changing product quantities with high quality, a fast time-to-market – these are the major challenges in the pharmaceutical and fine chemical industry. Thanks to this premium toolkit, developed by Lonza and exclusively distributed world-wide by Ehrfeld Mikrotechnik, active pharmaceutical ingredients (APIs) and fine chemicals can be researched and produced more competitively. In fact, campaign-based on-demand production under cGMP conditions and production up to ton scale are available within a very short time. High pressure resistance up to 100 bar offers new process windows for users. The compact design can be expanded modularly; plates with different channel design can be replaced easily, even in the case of a built-in reactor. The plate design can be flexibly adjusted to specific customer requirements and process tasks. The Cleaning-In-Place (CIP) process is easy to apply thanks to the process channel, which is free from dead volume with a closed and seal-free single-channel design.
During the practical session, we will demonstrate a fully automated multi-step organometallic reaction in our modular platform MMRS including the FlowPlate® Lab reactor – the smallest in the range but superbly equipped: it is optimally suited for feasibility studies in the laboratory, process development and pre-clinical research especially for multi-step synthesis. The exchangeable micro-structured process plate contains up to 10 inlets and outlets along the reaction channel. This ensures high flexibility for a variety of different processes. The flow process in the entire channel can be visually monitored through a sight glass. The real-time in-process monitoring of the reaction will be shown using various integrated sensors topped with an inline NIR. In our chosen model reaction, the deprotonation of tert-butyl propionate by LDA will be monitored using the inline NIR. Here, the disappearance of the ester C=O stretch can be clearly quantified. The second part of the reaction of the formed enolate with an aldehyde will lead the metallated intermediate. A subsequent in-situ quench with water generates the desired aldol product. Organometallic reactions are widely used in the pharmaceutical industry for the API production. These reactions are characterized by fast reaction speed, high exothermicity and low reaction temperatures due to kinetic driven byproducts. The use of the MMRS reactor platform with integrated PAT enables a fast and easy way to optimize reactions in terms of yield, selectivity and conversion at significant higher reaction temperatures.