Crystallization is usually a highly selective process, and this selectivity is exploited in the pharmaceutical and other industries as a method of chemical purification. Relatively little is known about how polymorphism and solvate formation can influence the selectivity of crystallizations. We describe a piperidene pharmaceutical intermediate that can crystallize as either a hydrate or an anhydrous form, with very different purities. The exploitation of this effect is described, and an explanation in terms of the crystal structures is proposed.

The intramolecular Diels−Alder reaction provides a useful synthetic methodology to build biologically active and synthetically useful isoindolone ring systems. An application of this methodology, providing an efficient manufacturing route to an mGluR2 positive allosteric modulator via a 1,5,7-substituted isoindolone, is reported herein.

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