(1SR,3RS,3aSR,6aRS)-Methyl 5-methyl-4,6-dioxo-3-[2-(trifluoro­meth­yl)phen­yl]octa­hydro­pyrrolo­[3,4-c]pyrrole-1-carboxyl­ate

Konstantin V Kudryavtsev; Polina M Ivantcova; Andrei V Churakov

doi:10.1107/S1600536812051471

. 2013 Jan 4;69(Pt 2):o161–o162. doi: 10.1107/S1600536812051471

(1SR,3RS,3aSR,6aRS)-Methyl 5-methyl-4,6-dioxo-3-[2-(trifluoromethyl)phenyl]octahydropyrrolo[3,4-c]pyrrole-1-carboxylate

Konstantin V Kudryavtsev ^a,^b,^*, Polina M Ivantcova ^a, Andrei V Churakov ^c

PMCID: PMC3569227 PMID: 23424450

Abstract

In the title compound, C₁₆H₁₅F₃N₂O₄, the relative stereochemistry of the four stereogenic C atoms has been determined. The carboxymethyl and 2-(trifluoromethyl)phenyl substituents of the pyrrolidine cycle have a cis mutual arrangement. The five-membered saturated azacycle adopts an envelope conformation with the N atom occupying the flap position. In the crystal, adjacent molecules are combined in centrosymmetric dimers by two weak N—H⋯O hydrogen bonds.

Related literature

For general background to the chemistry affording bicyclic pyrrolo[3,4-c]pyrrole-based scaffolds and structural determination, see: Kudryavtsev & Irkha (2005 ▶); Kudryavtsev (2008 ▶); Kudryavtsev & Zagulyaeva (2008 ▶); Kudryavtsev et al. (2011 ▶).

Experimental

Crystal data

C₁₆H₁₅F₃N₂O₄
M _r = 356.30
Orthorhombic,
a = 11.6168 (4) Å
b = 12.7385 (5) Å
c = 21.2429 (8) Å
V = 3143.5 (2) Å³
Z = 8
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 150 K
0.35 × 0.30 × 0.25 mm

Data collection

Bruker SMART APEXII diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.955, T _max = 0.968
28987 measured reflections
4585 independent reflections
3698 reflections with I > 2σ(I)
R _int = 0.032

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.115
S = 1.05
4585 reflections
286 parameters
All H-atom parameters refined
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.36 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supplementary Material

Click here for additional data file.^{(23.4KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812051471/ff2094sup1.cif

e-69-0o161-sup1.cif^{(23.4KB, cif)}

Click here for additional data file.^{(224.7KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812051471/ff2094Isup2.hkl

e-69-0o161-Isup2.hkl^{(224.7KB, hkl)}

Click here for additional data file.^{(6.5KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536812051471/ff2094Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O3ⁱ	0.884 (15)	2.363 (15)	3.1738 (13)	152.5 (13)

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

This study was partially supported by the Russian Foundation for Basic Research (project Nos 11-03-00630_a, 11-03-91375-ST_a and 12-03-92005-NNS_a).

supplementary crystallographic information

Comment

The core of the title compound is formed by two fused pyrrolidine cycles. It was effectively synthesized by the three-component approach developed by the authors (Fig. 1). Combination of molecular sieves and triethyamine represents an efficient reagent for performing three-component interaction of benzaldehyde, glycine ester and dipolarophile. The product X-ray structure determination indicates that cycloaddition step proceeds as endo-process (Fig. 2). Tetrasubstituted pyrrolidine cycle adopts envelope conformation with N1 atom occupying flap position. Amine atom N1 has trigonal pyramidal environment with the sum of valent angles equal to 329.0 °. Hydrogen atom H1 lies in axial position (relative to the mean plane of five-membered ring). As expected, dioxopyrrolidine cycle is planar within 0.0354 (7) Å.

In the crystal, the adjacent molecules are combined in centrosymmetric dimers by two weak N—H···O hydrogen bonds (Fig. 3). The same dimers were previously observed in the structure of (1SR,3RS,3aSR,6aRS-methyl 5-methyl-4,6-dioxo-3-phenyloctahydropyrrolo [3,4-c]pyrrole-1-carboxylate (Kudryavtsev & Zagulyaeva, 2008).

Experimental

Triethylamine (0.340 ml, 2.41 mmol) was added to the stirred mixture of 2-(trifluoromethyl)benzaldehyde (200 mg, 1.15 mmol), N-methylmaleimide (130 mg, 1.15 mmol), glycine methyl ester hydrochloride (158 mg, 1.30 mmol) and 4 Å molecular sieves (200 mg) in toluene under argon atmosphere. Reaction mixture was stirred for 48 h. Volatiles were removed at reduced pressure. CH₂Cl₂ (50 ml) was added to the residue, resulted suspension was filtered through Celite, washed with saturated solution of NH₄Cl (2 x 10 ml). Organic phase was dried over Na₂SO₄, concentrated and purified by column chromatography on silica gel 60 (particle size 0.040–0.063 mm) using CH₂Cl₂—MeOH (100:1) as eluent. Yield 168 mg (41%), colorless crystals, mp 183–185°C. ¹H NMR (400 MHz, CDCl₃): δ 2.61 (s, 3H, NCH₃), 3.28 (t, 1H, H-3a, J 8.2), 3.40 (t, 1H, H-6a, J 7.3), 3.64 (s, 3H, OCH₃), 3.95 (d, 1H, H-1, J 6.7), 4.59 (d, 1H, H-3, J 8.6), 7.20 (t, 1H, Ar, J 7.6), 7.30 (t, 1H, Ar, J 7.6), 7.61 (d, 1H, Ar, J 7.6). ¹³C NMR (100 MHz, CDCl₃): δ 24.94, 47.31, 48.92, 52.26, 58.89, 61.04, 123.02, 125.89, 128.06, 128.23, 131.96, 135.74, 169.84, 174.30, 175.78. Found, %: C, 54.12; H, 4.27; N, 7.78. C₁₆H₁₅F₃N₂O₄. Calculated, %: C, 53.94; H, 4.24; N, 7.86. The crystals were obtained by slow evaporation of the CDCl₃ solution.