Crystal structure of methyl (4R)-4-(4-methoxybenzoyl)-4-{[(1R)-1-phenylethyl]carbamoyl}butanoate

The CAN oxidation of a β-lactam leads to a 4-substituted glutarate. In the crystal, amide-C(4) N—H⋯O and reinforcing C—H⋯O hydrogen bonds link the molecules into infinite [010] chains. Further C—H⋯O hydrogen bonds cross-link the chains in the c-axis direction.


Chemical context
Cerium(IV) ammonium nitrate (CAN) is a powerful reagent in organic synthesis, which promotes a wide range of reactions that go well beyond its usual role as an oxidant (Sridharan & Menendez, 2010). Chemoselective mono-debenzylation of benzyl tertiary amines occurs in the presence of N-benzyl amides, O-benzyl ethers and esters (Bull et al., 2000); interestingly this reaction can be applied to mono-debenzylation of -amino esters as a way to obtain -lactams (Davies & Ichihara, 1998) or piperidone (Garrido et al., 2011), providing as well a new oxidative methodology as catch linker for reaction monitoring and optimization on solid phase support (Davies et al., 2008). Our group has demonstrated two different domino reactions, one by lithium amide addition to diendioate that can be applied to the synthesis of cyclopentanic (Urones et al., 2004) or cyclohexanic (Garrido et al., 2006) derivatives and the other by addition to Baylis-Hillman (Garrido et al., 2008) derivatives with application to the synthesis of non-peptidic neurokinin NK1 receptor antagonist (+)-L-733,060 (Garrido et al., 2010). Within this context of the synthesis of biologically active compounds, we are interested in the synthesis of -lactam and its mono-deprotection, as shown in the Scheme, where the asymmetric 4-benzoyl glutarate is readily obtained by CAN oxidation of the appropriate substituted -lactam. For the CAN oxidation reaction of a related trialkyl amine derivative providing monodeprotection, see Garrido et al. (2011).

Structural commentary
The molecular structure of the title compound is shown in Fig. 1. The molecule consists of an ester amide glutarate derivative with a p-metoxybenzoyl group as substituent: all the bond lengths and angles are within normal ranges. The almost planar conformation of the ester group is established from the torsion angle C20-C21-O4-C22 of 178.6 (3) . The ether group atom C1 and the carbonyl group atom C8 are almost coplanar with the benzene ring, the C7-O1-C1-C6 and O2-C8-C4-C5 torsion angles being 177.9 (1) and 172.4 (8) , respectively. The C11 methyl group is also almost coplanar with the its benzene ring, as indicated by the torsion angle C18-C11-C12-C13 of 176.68 (7) . The dihedral angle between the aromatic rings is 13.3 (4) .

Supramolecular features
In the extended structure of the title compound, hydrogen bonds are one of the primary factors in building the crystal network (Table 1). Intermolecular N1-H1Á Á ÁO3 i (dotted light-blue lines), C9-H9Á Á ÁO3 i dotted (orange lines) and C20-H20AÁ Á ÁO2 i (dotted blue lines) hydrogen bonds link neighboring molecules, generating infinite chains running along the b-axis direction (Fig. 2). These chains are joined to each other along c axis by C17-H17Á Á ÁO5 ii interactions (dotted pink lines), as shown in Fig. 3. The packing viewed along the [010] direction is illustrated in Fig. 4. The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radius. Symmetry codes: (i) x; y þ 1; z; (ii) Àx; y þ 1 2 ; Àz þ 5 2 .

Figure 3
A view of the C17-H17Á Á ÁO5 (dotted pink lines) hydrogen bonds in the extended structure of the title compound.

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. 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 > 2sigma(F 2 ) is used only for calculating R-factors(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.