Methyl (R)-2-(2-chloro­phen­yl)-2-(3-nitro­phenyl­sulfon­yloxy)acetate

Ying-Hua Li; Hong-Wu Xu; Liu-Xue Zhang

doi:10.1107/S1600536812020016

. 2012 May 12;68(Pt 6):o1689. doi: 10.1107/S1600536812020016

Methyl (R)-2-(2-chlorophenyl)-2-(3-nitrophenylsulfonyloxy)acetate

Ying-Hua Li ^a, Hong-Wu Xu ^a,^*, Liu-Xue Zhang ^a

PMCID: PMC3379285 PMID: 22719483

Abstract

The reaction between methyl (R)-2-(2-chlorophenyl)-2-hydroxyacetate and 3-nitrobenzenesulfonyl chloride gave the title compound, C₁₅H₁₂ClNO₇S, which is a promising intermediate for the synthesis of Clopidrogel, an antiplatelet drug used in the prevention of strokes and heart attacks. In the crystal, molecules are linked through C—H⋯O interactions, and there is also a short Cl⋯O contact present [Cl⋯O = 3.018 (2) Å].

Related literature

For the synthesis of (R)-2-(2-chlorophenyl)-2-hydroxyacetic acid, see: Bousquet & Musolino (2003 ▶). For related structures, see: Sun et al. (2007 ▶); Andersen et al. (2007 ▶). For the synthesis of Clopidrogel from sulfonyloxyacetic esters of (R)-2-(2-chlorophenyl)-2-hydroxyacetic acid, see: Bousquet & Musolino (1999 ▶); Castaldi et al. (2003 ▶); Ema et al. (2007 ▶); Zhu et al. (2010 ▶). For halogen bonds, see: Bianchi et al. (2004 ▶); Fourmigue (2009 ▶); Metrangolo et al. (2005 ▶). graphic file with name e-68-o1689-scheme1.jpg

Experimental

Crystal data

C₁₅H₁₂ClNO₇S
M _r = 385.77
Orthorhombic,
a = 7.5791 (3) Å
b = 11.0242 (5) Å
c = 19.6736 (7) Å
V = 1643.80 (11) Å³
Z = 4
Mo Kα radiation
μ = 0.40 mm⁻¹
T = 293 K
0.30 × 0.25 × 0.22 mm

Data collection

Agilent Xcalibur Eos Gemini diffractometer
Absorption correction: multi-scan (Crysalis PRO; Agilent, 2011 ▶) T _min = 0.890, T _max = 0.918
5654 measured reflections
3153 independent reflections
2680 reflections with I > 2σ(I)
R _int = 0.023

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.086
S = 1.02
3153 reflections
227 parameters
H-atom parameters constrained
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.21 e Å⁻³
Absolute structure: Flack (1983 ▶), 1209 Friedel pairs
Flack parameter: 0.07 (7)

Data collection: Crysalis PRO (Agilent, 2011 ▶); cell refinement: Crysalis PRO; data reduction: Crysalis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL/PC (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL/PC and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812020016/zl2477sup1.cif

e-68-o1689-sup1.cif^{(17.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812020016/zl2477Isup2.hkl

e-68-o1689-Isup2.hkl^{(154.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812020016/zl2477Isup3.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
C14—H5⋯O4	0.93	2.55	2.920 (4)	104
C14—H5⋯O1ⁱ	0.93	2.60	3.323 (4)	135
C15—H8C⋯O5ⁱⁱ	0.96	2.53	3.419 (4)	155

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

This work was supported by the Program for Science and Technology Innovation Talents at the Universities of Henan Province (grant No. 2011HASTIT022).

supplementary crystallographic information

Comment

Sulfonyloxyacetic esters of (R)-methyl-2-(2-chlorophenyl)-2-hydroxyacetate are commonly used in the synthesis of Clopidrogel, an antiplatelet drug used in the prevention of strokes and heart attacks (sold in the United States under the brand name of Plavix) (Bousquet & Musolino, 1999; Castaldi et al., 2003; Ema et al., 2007; Zhu et al., 2010). The title compound, a promising intermediate for the synthesis of Clopidrogel, was obtained in two steps from (R)-2-(2-chlorophenyl)-2-hydroxyacetic acid (Bousquet & Musolino, 2003). We report here its crystal structure. In the molecule of the title compound (Fig. 1), the main bond lengths and angles are close to those found in some other derivatives of (R)-methyl-2-(2-chlorophenyl)-2-hydroxyacetate (for example, (R)-methyl-2-(2-chlorophenyl)-2-(benzenesulfonyloxy) acetate and 4aR,11R,11aS)-11-methyl-9- (trifluoromethyl)-1,2,2,3,4,4a,5,6,11,11adecahydro-pyrido[4,3-b] carbazole (R)-2-chloromandelate (Sun et al., 2007; Andersen et al., 2007). The crystal structure of this compound is stabilized by an intermolecular halogen bond (Bianchi et al., 2004; Fourmigue, 2009; Metrangolo et al., 2005) between the Cl atom and one of the O atoms of the SO₂ group of an adjacent molecule, with a C4–Cl1···O4ⁱ separation of 3.018 (2) Å (Fig. 2 and Table 1). Symmetry code (i): x - 1, y, z. The crystal structure is also stabilized by intermolecular C–H···O hydrogen bonding interactions (Table 1).

Experimental

(R)-2-(2-Chlorophenyl)-2-hydroxyacetic acid and (R)-methyl-2- (2-chlorophenyl)-2-hydroxyacetate were prepared using the established literature procedures (Bousquet et al., 2003, and Sun et al., 2007). A three-necked round-bottomed flask, which was equipped with a magnetic stir bar, was charged with dichloromethane (50 ml), (R)-methyl-2- (2-chlorophenyl)-2-hydroxyacetate (4.5 g), triethylamine (4.3 g), and 4,4-dimethylaminopyridine (275 mg). 3-Nitrobenzenesulfonyl chloride (5.5 g) and dichloromethane (50 ml) were added via syringe. The mixture was stirred at room temperature for 3 h. The reaction mixture was quenched with water, and washed with 1 N HCl (30 ml) twice. The organic layer was dried over anhydrous sodium sulfate and filtered. After concentration under reduced pressure, the residue was purified by silica gel column chromatography with a mixture of petroleum ether and ethyl acetate (4:1 v/v) as eluent to give the title compound (yield, 54%). ¹H NMR (400 MHz, CDCl₃): 8.648 (s, 1H), 8.432 (d, J = 8.0 Hz, 1H), 8.208 (d, J = 8.0 Hz, 1H), 7.704 (t, J = 8.0 Hz, 1H), 7.376 (d, J = 8.0 Hz, 1H), 7.319 - 7.206 (m, 3H), 6.394 (s, 1H), 3.765 (s, 3H) p.p.m.. Well shaped colorless crystals were obtained by slow evaporation of a solution in petroleum ether and ethyl acetate at room temperature for a few days.