Volume intensified dilution of a ring-closing metathesis in ethyl acetate by means of a membrane-assisted process in solvent recycle

BACKGROUND Ring-closing metathesis (RCM) for the synthesis of macrocycles has been used more and more often over recent years, including some interesting applications on industrial scale. However, like all macrocyclization strategies RCM is plagued by the traditional issue of low volume efficiency. To-date this is typically addressed in a molecule specific manner with varying degrees of success. Here we report a process intensification method of metathesis macrocyclization that reduces the solvent load required for the reaction significantly. RESULTS Metathesis macrocylizations were successfully carried out in a solvent volume of upto 82% lower than an equivalent batch reaction, with only minimal impact upon the reaction outcome. A switch of reaction solvent to ethyl acetate renders the process more benign and applicable to large scale. CONCLUSION A membrane-assisted processing method that relies upon organic solvent nanofiltration permitting an internal solvent recycling and concumittent in situ product removal. The method is also designed to be applicable to a wide range of metathesis cyclizations. (c) 2019 Society of Chemical Industr

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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