Eplerenone ethanol solvate

Eplerenone [systematic name: 7α-(methoxycarbonyl)-3-oxo-9α,11-epoxy-17α-pregn-4-ene-21,17-carbolactone], an aldosterone receptor antagonist, crystallizes from ethanol as a monosolvate, C24H30O6·C2H6O. The eplerenone molecule has two five-membered rings, three six-membered rings and one three-membered ring. Both five-membered rings display envelope conformations, while the three six-membered rings assume envelope (cyclohexene), half-chair (cyclohexane sharing one edge with epoxy) and chair (other cyclohexane) conformations. The solvent molecule is disordered equally over two sites. It is linked to the eplerenone molecule by hydrogen bonds.


Comment
The eplerenone is known as an aldosterone receptor antagonist and can be administered in a therapeutically effective amount where use of an aldosterone receptor antagonist (Grob et al., 1985). The crystal structure of the eplerenone ethanol solvate is reported here.
The crystal of the title compound consists of eplerenone molecules and lattice ethanol molecules (Fig. 1). The molecule of eplerenone contains three six-membered rings, two five-membered rings and one three-membered ring. A ring analysis (Spek, 2003) indicates that three six-membered rings assume different conformations: chair, half-chair and envelope; both five-membered rings display the similar envelope configuration. This agrees with those found in the structure of eplerenone THF solvate (Yang et al. 2007) and in the structure of eplerenone dioxane solvate (Xu et al., 2007). The C2-C3 bond distance of 1.343 (6) Å indicates the typical C?C double bond. The C23-ester group forms an intra-molecular C-H···O hydrogen bond with the adjacent C14-methine group (Table 1). This structural feature is also found in the crystal structure of eplerenone dichloromethane solvate (Grob et al., 1997).
In the crystal structure, lattice solvent molecules are disorderly located in the cavities formed by eplerenone molecules and link with eplerenone molecules via O-H···O and C-H···O hydrogen bonding (Table 1).

Experimental
A microcrystalline powder sample of eplerenone was prepared in the manner reported by Grob et al. (1997). Single crystals of the title compound were obtained from an ethanol solution of eplerenone.

Refinement
The lattice ethanol molecule is disordered in the crystal structure; a two-site model with each 0.5 site occupancies was adopted in the refinement. The C-C and C-O distances for the disordered solvent molecule were constrained to 1.50±0.01 and 1.40±0.01 Å, respectively; atomic displacement parameters for non-H atoms of the disordered solvent molecule were constrained to be the same. Hydroxyl H atoms were placed in chemical sensible positions and refined in riding mode with U iso (H) = 1.5U eq (O). Other H atoms were placed in calculated positions with C-H = 0.93 to 0.98 Å, and refined in riding mode with U iso (H) = 1.5U eq (C) for methyl or 1.2U eq (C) for others. In the absence of significant anomalous scattering effects, Friedel pairs were merged; the absolute configuration was not determined.
supplementary materials sup-2 Figures Fig. 1. The molecular structure of the title compound with 30% probability displacement (arbitrary spheres for H atoms). One of disordered solvent components has been omitted for clarity.

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.