The Zymark BenchMate™. A compact, fully-automated solution-phase reaction work-up facility for multiple parallel synthesis

摘要

The rapid growth of multiple parallel synthesis in our laboratories has created a demand for a robust, easily accessed automated system for solution-phase reaction work-up, since the manual work-up of large numbers of small-scale reactions is both time-consuming and tedious, and is a rate limiting step in the generation of large numbers of compounds for test. Work-up in chemical organic synthesis consists of a series of post-reaction operations designed using differential chemical properties to remove excess reagent or starting material, reagent products and, where possible reaction by-products. Careful consideration of post-reaction operations as a clean-up step can obviate the requirement for purification. Generally, work-up can be resolved into four operations: filtration, solvent addition (dilution, trituration), washing and separation (partition) and it is the selection and ordering of these four basic operations that constitutes a chemical work-up. Following the proven success of centralized Zymate robotic systems in the compilation, execution and work-up of complex reaction sequences, a centralized chemical work-up service has been in operation for over 12 months. It now seemed prudent that the needs of multiple parallel synthesis would be better served by the development of a compact, automated system, capable of operating in a standard chemistry laboratory fume-hood. A Zymark BenchMate platform has been configured to perform the four basic operations of chemical solution work-up. A custom-built filtration station, incorporating an integrated tipping facility for the sample tube has also been developed. Compilation of each work-up is through a set of Visual Basic procedure screens, each dedicated to a particular work-up scenario. Methods are compiled at the chemist's own PC and transferred to the BenchMate via a diskette.