NMR and polymorphism of a piperidinone-substituted benzopyran with a fluorinated sidechain

Abstract

Two polymorphs of (3S-trans)-1-[3,4-dihydro-3-hydroxy-2,2-dimethyl-6-(pentafluoroethyl)-2H-1-benzopyran-4-yl]piperidin-2-one (A)‡ have been characterised by solid-state ¹³C and ¹⁹F cross-polarisation magic-angle spinning NMR, aided by IR spectroscopy, differential scanning calorimetry and X-ray powder diffraction methods. The two polymorphs show markedly different NMR spectral phenomena, including variations in residual dipolar coupling characteristics and crystallographic splitting of resonances, indicating that more than one molecule exists in the asymmetric unit of polymorphic form II. The ¹³C NMR studies involved triple-channel operation, with simultaneous decoupling of ¹H and ¹⁹F, including cross polarisation from ¹⁹F as well as from ¹H. Dual-channel ¹⁹F measurements have been carried out using ¹H decoupling, with cross polarisation from ¹H.