Methyl 1-benzyl-5-methyl-2,4-diphenyl-1H-pyrrole-3-carboxylate

In the title compound, C26H23NO2, the dihedral angles between the pyrrole ring and the two phenyl rings are 58.1 (6) and 71.5 (5)°. The mean planes of the 5-methylbenzene ring and the carboxyl group are twisted by 89.5 (3) and 22.1 (9)°, respectively, from the pyrrole ring. In the crystal, weak C—H⋯O interactions lead to supramolecular layers in the ab plane.

In the title compound, C 26 H 23 NO 2 , the dihedral angles between the pyrrole ring and the two phenyl rings are 58.1 (6) and 71.5 (5) . The mean planes of the 5-methylbenzene ring and the carboxyl group are twisted by 89.5 (3) and 22.1 (9) , respectively, from the pyrrole ring. In the crystal, weak C-HÁ Á ÁO interactions lead to supramolecular layers in the ab plane.
JML acknowledges support from a Graduate Assistance in Areas of National Need (GAANN) fellowship. GWG acknowledges support by the Donors of the Petroleum Research Fund (PRF), administered by the American Chemical Society, and by Wyeth. JPJ acknowledges the NSF-MRI program (grant No. CHE-1039027) for funds to purchase the X-ray diffractometer.

Structural commentary
During the course of our studies toward a total synthesis of atorvastatin, methyl 1-benzyl-5-methyl-2,4-diphenyl-1Hpyrrole-3-carboxylate (I), a pentasubstituted pyrrole, was generated from the reaction of a münchnone with methyl 3phenylpropiolate. Previously published work on münchnone-based routes toward atorvastatin found that the key münchnone cycloadditions were either low yielding or unselective and delivered 1:1 mixtures of regioisomers (Pandey et al., 2004;Park et al., 2008;Roth et al., 1991). However, our recent studies on the 1,3-dipolar cycloaddition of münchnones showed that high regioselectivies can be obtained by proper selection and combination of the münchnone, dipolarophile, and solvent (Lopchuk et al., 2011a, Lopchuk et al., 2011bLopchuk et al., 2013).

Synthesis and crystallization
A round bottom flask was charged with N-benzoyl-N-benzylalanine (424 mg, 1.5 mmol), methyl 3-phenylpropiolate (80 mg, 0.5 mmol), and dry THF (20 ml). The reaction was placed under nitrogen and N,N′-diisopropylcarbodiimide (234 ml, 1.5 mmol) added at room temperature. The mixture was heated to reflux for 24 h (Fig. 2). The reaction was cooled to room temperature and concentrated in vacuo. The residue was directly purified by flash chromatography to afford pyrrole I as a clear, colorless oil which solidified upon standing (158 mg, 83%). Pyrrole I was obtained as the major isomer (

Refinement
All of the H atoms were placed in their calculated positions and then refined using the riding model with atom-H lengths of 0.95 Å (CH), 0.99 Å (CH 2 ) or 0.98 Å (CH 3 ). Isotropic displacement parameters for these atoms were set to 1.2 (CH, CH 2 ) or 1.5 (CH 3 ) times U eq of the parent atom. Idealized methyl groups were refined as rotating.

Figure 2
Reaction scheme for C 26 H 23 NO 2 .