Journal
DRUG DISCOVERY TODAY
Volume 22, Issue 1, Pages 133-139Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2016.09.018
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A strategy for large-scale chiral resolution is illustrated by the isolation of pure enantiomer from a 5 kg batch. Results from supercritical fluid chromatography will be presented and compared with normal phase liquid chromatography. Solubility of the compound in the supercritical mobile phase was shown to be the limiting factor. To circumvent this, extraction injection was used but shown not to be efficient for this compound. Finally, a method for chiral resolution by crystallization was developed and applied to give diastereomeric salt with an enantiomeric excess of 99% at a 91% yield. Direct access to a diverse separation tool box will be shown to be essential for solving separation problems in the most cost and time efficient way.
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