(S)-Methyl 2-benzamido-3-(3,4-dimeth­oxy­phen­yl)propano­ate

Tricia Naicker; Thavendran Govender; Hendrick G Kruger; Glenn E M Maguire

doi:10.1107/S1600536811052767

. 2011 Dec 21;68(Pt 1):o177. doi: 10.1107/S1600536811052767

(S)-Methyl 2-benzamido-3-(3,4-dimethoxyphenyl)propanoate

Tricia Naicker ^a, Thavendran Govender ^a, Hendrick G Kruger ^b, Glenn E M Maguire ^b,^*

PMCID: PMC3254516 PMID: 22259461

Abstract

The dimethoxypbenzene ring in the title compound, C₁₉H₂₁NO₅, is gauche to the amide group and anti to the ester group. The chirality was confirmed to be S from two-dimensional NMR spectroscopy. In the crystal, N—H⋯O and C—H⋯O hydrogen bonds and several short-contact interactions (2.07–3.45 Å) create chains parallel to [110]. The phenyl ring is disordered over two orientations in a 0.54 (2):0.46 (2) ratio.

Related literature

The title compound is a precusor to novel chiral organocatalyts. For the synthesis, see: Naicker et al. (2011 ▶) and for related structures, see: Clegg & Elsegood (2003 ▶); Zalán et al. (2006 ▶)

Experimental

Crystal data

C₁₉H₂₁NO₅
M _r = 343.37
Monoclinic,
a = 20.331 (9) Å
b = 5.070 (3) Å
c = 17.580 (9) Å
β = 108.489 (8)°
V = 1718.5 (15) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 173 K
0.75 × 0.05 × 0.03 mm

Data collection

Bruker Kappa DUO APEXII diffractometer
3865 measured reflections
1645 independent reflections
930 reflections with I > 2σ(I)
R _int = 0.077

Refinement

R[F ² > 2σ(F ²)] = 0.077
wR(F ²) = 0.219
S = 0.99
1645 reflections
263 parameters
13 restraints
H-atom parameters constrained
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.35 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶; data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811052767/hg5150sup1.cif

e-68-0o177-sup1.cif^{(21.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811052767/hg5150Isup2.hkl

e-68-0o177-Isup2.hkl^{(81.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811052767/hg5150Isup3.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⋯O5ⁱ	0.88	2.07	2.924 (9)	163
C2—H2⋯O5ⁱ	0.95	2.55	3.412 (11)	151

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors wish to thank Dr Hong Su of the Chemistry Department of the University of Cape Town for her assistance with the crystallographic data collection.

supplementary crystallographic information

Comment

The title compound is a well known precusor to several biologically active compounds (Zalán et al., 2006). In our laboratory it is being used as a precusor to novel chiral organocatalyts (Naicker et al. 2011).

There is only one analogous X-ray crystal structure that has a tertiary butyl group at the C12 position and a O—CH₂-fluorenyl group is attached to the carbonyl carbon at C13 (Clegg & Elsegood, 2003). The title compound exists in a perfectly staggered conformation about the C9—C10 bond (Fig. 1). Similar to the analogous X-ray structure, the dimethoxyphenyl ring is gauche to the amide group and anti to the ester group.

The initial starting material for the synthesis of the title compound was optically pure L-DOPA, the chirality at the C8 atom remained unchanged during the synthesis and was confirmed to be S configuration from two-dimensional NMR spectroscopy.

The molecules in the crystal are connected by N1—H1···O5 (2.07 (9) Å) hydrogen bonds (Fig. 2), supported by a weak C2—H2···O5 (2.54 (11) Å) hydrogen bond from the dimethoxyphenyl ring which form chains parallel to the 110 plane (Table 2). In the analogous structure the same hydrogen bonds, have lengths of 2.36 Å and 2.42 Å respectively. In addition, there are several intermolecular short contact interactions (2.07–3.45 Å) within the crystal packing.

The phenyl ring is disordered with two orientations at 50% site occupancy.

Experimental

Benzoic acid (0.5 g, 4.2 mmol) was dissolved was dissolved in DMF (15 ml) and THF (5 ml) followed by addition of HBTU (4.6 mmol), DIPEA (8.4 mmol) and (S)-methyl 2-amino-3-(3,4-dimethoxyphenyl)propanoate (1.0 g, 4.2 mmol). The reaction mixture was then stirred at room temperature until no more starting material could be detected by TLC analysis. The reaction mixture was poured into 30 volumes of chilled water; the mixture was then extracted thrice with ethyl acetate (20 ml). The combined extracts were dried over anhydrous sodium sulfate and then concentrated to dryness affording the crude product. This crude product was purified by column chromatography (50:50 EtOAc/Hexane, Rf = 0.6) to afford the product 1.30 g (92%) as a white solid. Melting point: 377–379 K.

Recrystallization from ethyl acetate at room temperature afforded crystals suitable for X-ray analysis.