Ethyl 3,4-bis(acetyloxy)-2-(4-methoxyphenyl)pyrrolidine-1-carboxylate

The title compound features a twisted, tetra-substituted pyrrolidine ring, and has an N-bound ethylcarboxylate substituent with the N atom flanked by a methylene group on one side and a C-bound 4-methoxyphenyl group on the other. These carbon atoms are linked by two methine carbon atoms, each of which bears an acetyloxy substituent.

The title pyrrolidine compound, C 18 H 23 NO 7 , is a tetra-substituted species in which the five-membered ring has a twisted conformation with the twist occurring in the C-C bond bearing the adjacent acetyloxy substituents; the C m -C a -C a -C p torsion angle is À40.76 (18) [m = methylene, a = acetyloxy and p = phenyl]. The N atom, which is sp 2 -hybridized [sum of bond angles = 359.4 ], bears an ethylcarboxylate substitutent and is connected to a methylene-C atom on one side and a carbon atom bearing a 4-methoxyphenyl group on the other side. Minor disorder is noted in the ethylcarboxylate substituent as well as in one of the acetyloxy groups; the major components of the disorder have site occupancies of 0.729 (9) and 0.62 (3), respectively. The most notable feature of the molecular packing is the formation of helical, supramolecular chains aligned along the b-axis direction whereby the carbonyl-O atom not involved in a disordered residue accepts C-HÁ Á ÁO interactions from methylene-H and two-C atom separated methine-H atoms to form a six-membered {Á Á ÁHCCCHÁ Á ÁO} synthon.

Structure description
As reviewed recently, -glucosidase inhibitors comprise a significant class of drugs as these are used for the treatment various disease including, among others, diabetes, cancer, cystic fibrosis and influenza (Kiappes et al., 2018;Dhameja & Gupta, 2019). It was data reports in this connection that the structure of the title tetra-substituted pyrrolidine derivative, (I), was determined in the context of supporting studies designed to provide conformational details of the molecular structures of crucial synthetic intermediates in the generation of various -glucosidase inhibitors (Zukerman-Schpector et al., 2017;Dallasta Pedroso et al., 2020a;Dallasta Pedroso et al., 2020b).
The molecular structure of (I), Fig. 1, features a fivemembered pyrrolidine ring scaffold which is tetra-substituted. Thus, N1 carries a ethylcarboxylate group, each of the methine-C2 and C3 atoms carries an acetyloxy substituent and finally, the methine-C4 atom carries a 4-methoxyphenyl group. The substitution pattern indicates the presence of three chiral centres. For the illustrated molecule in Fig. 1, the chirality of the C2-C4 atoms follows the sequence R, S and S. However, it should be noted the centrosymmetric unit cell of (I) contains equal numbers of the S, R, R enantiomer. The conformation of the five-membered ring is best described as being twisted about the C2-C3 bond as seen in the value of the C1-C2-C3-C4 torsion angle of À40.76 (18) , which is consistent with a (À)syn-clinal configuration. The relative orientations of the non-H substituents at the N1, C2-C4 atoms about the ring are equatorial, axial, equatorial and bisectional, respectively (Spek, 2020). The sum of the angles about the N1 atom comes to 359.4 , being indicative of an approximate sp 2 centre. While globally, to a first approximation, the substituents at N1 and C3 lie in the plane of the ring, the substituents at the C1 and C4 atoms lie to either side of the five-membered ring.
The substitution pattern in pyrrolidine (I) is comparatively rare with the most closely related structures being only recently reported. In one derivative, the difference arises as the N1-bound substituent is a 4-nitrophenylmethyl group while the other groups are the same (Dallasta Pedroso et al., 2020a) while in the other, only the substituent at the C4 differs, with the literature structure having a methylcarboxylate group (Dallasta Pedroso et al., 2020b).
Owing to the presence of disorder in the residues bound at the N1 and C3 atoms, a detailed analysis of the molecular packing is problematic. However, supramolecular chains propagating along the b-axis direction may be discerned, Fig. 2(a). These have a helical topology being generated by 2 1screw symmetry and arise as the carbonyl-O1 accepts two C-HÁ Á ÁO interactions, Table 1, from the C1-methylene and C3methine substituents with the result that six-membered {Á Á ÁHCCCHÁ Á ÁO} synthons are apparent. A view of the unitcell contents showing the packing of chains is shown in Fig. 2 Table 1 Hydrogen-bond geometry (Å , ).

Figure 1
The molecular structure of (I), showing the atom-labelling scheme and displacement ellipsoids at the 35% probability level. The minor components of the disordered residues are omitted.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Two residues in the molecule were found to be disordered. Thus, the C7-methyl group of the N1bound substituent was disordered over two positions, as was the carbonyl-O4 atom of the C3-acetyloxy group. Each disorder component was refined independently and with anisotropic displacement parameters. The major components of the disorder refined to occupancies of 0.729 (9) and 0.62 (3), respectively.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ. (