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Racemic Conglomerate Formation via Crystallization of Metaxalone from Volatile Deep Eutectic Solvents
journal contribution
posted on 2020-06-17, 17:42 authored by Victoria Hamilton, Iryna Andrusenko, Jason Potticary, Charlie Hall, Richard Stenner, Enrico Mugnaioli, Arianna E. Lanza, Mauro Gemmi, Simon R. HallThe pharmaceutical
metaxalone (MTX) was obtained as a conglomerate
Form A-R/S, via a newly reported crystallization method exploiting
volatile deep eutectic solvents. Homochiral crystals of Form A-S could
previously be obtained only by crystallization from enantiopure MTX,
synthesized from enantiopure starting materials, and never from a
racemic solution of MTX. Powder X-ray diffraction and chiral high-performance
liquid chromatography were used to infer that the structure of the
crystals obtained was a conglomerate relating to the known Form A-S.
However, this pathway results in exclusively micron-sized needles,
below typical structural solution size, and so three-dimensional electron
diffraction, combining low-dose continuous acquisition and a dedicated
single-electron detector, was used for ab initio structural solution
of Form A-R/S. Crystallization via volatile deep eutectic solvents
allowed the structural landscape of metaxalone to be further explored,
adding a point to its phase diagram. This example highlights the possibility
for symbiotic relationships between structural solution via electron
diffraction and crystallization pathways which do not result in crystals
of a suitable size and quality for single-crystal X-ray diffraction.