Ethyl 1-benzyl-4-hydroxy-2-methyl-5-oxopyrrolidine-3-carboxylate

In the title oxopyrrolidine, C15H19NO4, the five-membered pyrrolidine ring is in a twist conformation and its mean plane makes an angle of 89.2 (3)° with the phenyl ring. In the crystal, molecules pack as dimers via strong O—H⋯O [R 2 2(10)] interactions cross-linked by weaker C—H⋯O and C—H⋯π interactions. Full synthetic and spectroscopic details are given for the title compound and related dicarboxylates.

In the title oxopyrrolidine, C 15 H 19 NO 4 , the five-membered pyrrolidine ring is in a twist conformation and its mean plane makes an angle of 89.2 (3) with the phenyl ring. In the crystal, molecules pack as dimers via strong O-HÁ Á ÁO [R 2 2 (10)] interactions cross-linked by weaker C-HÁ Á ÁO and C-HÁ Á Á interactions. Full synthetic and spectroscopic details are given for the title compound and related dicarboxylates.
We thank Professor Ward T Robinson and Dr J. Wikaira of the University of Canterbury, New Zealand, for their assistance.
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SJ2755).

Comment
The title oxopyrrolidine (I) (see Fig 3) was prepared as part of a programme to elucidate the structure-activity relationships of the Immucillin family of potent purine nucleoside phosphorylase inhibitors (Mason et al., 2007;Edwards et al., 2009. Cycloaddition of the nitrone formed from N-benzyl hydroxylamine and acetaldehyde to diethyl maleate forms racemic, isomeric, isoxazolidine dicarboxylates II and III in 3:1 ratio. Reductive cleavage of the major isomer(II) with zinc was accompanied by spontaneous lactam formation to give the crystalline racemic pyrrolidine (I): the (2R*,3R*,4S*) isomer in shown in Figure 1.
All other H atoms were placed in geometrically idealised positions and constrained to ride on their parent atoms with C-H distances of 0.95 (aromatic) or 0.99 (methylene) Å with U iso (H) = 1.2U eq (C). Two low angle reflections were omitted from the final cycles of refinement because their observed intensities were much lower than the calculated values as a result of being partially obscured by the beam stop. Five other reflections were identified as outliers and removed from refinement.
The crystals were minute in one direction, barely adequate but enough data was measured to solve the structure which met the chemical requirement for the study. Fig. 1. Molecular structure of (I) at the 50% ellipsoid probability level.  Macrae et al., 2006) showing the strong dimer-forming O-H···O interactions (Table 1). Fig. 3. Compounds formed during the synthesis of (I).
(II) (3S*,4S*,5R*)-Diethyl 2-benzyl-3-methylisoxazolidine-4, 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.
supplementary materials sup-4 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.