(R)-[1-(2-Chloro­phen­yl)-2-meth­oxy-2-oxoeth­yl][2-(thio­phen-2-yl)eth­yl]ammonium (+)-camphor-10-sulfonate acetone monosolvate

Yan-Shu Liang; Shuai Mu; Ying Liu; Deng-Ke Liu

doi:10.1107/S160053681004523X

. 2010 Nov 10;66(Pt 12):o3117. doi: 10.1107/S160053681004523X

(R)-[1-(2-Chlorophenyl)-2-methoxy-2-oxoethyl][2-(thiophen-2-yl)ethyl]ammonium (+)-camphor-10-sulfonate acetone monosolvate

Yan-Shu Liang ^a, Shuai Mu ^b, Ying Liu ^c,^*, Deng-Ke Liu ^c

PMCID: PMC3011721 PMID: 21589421

Abstract

The title compound, C₁₅H₁₇ClNO₂S⁺·C₁₀H₁₅O₄S⁻·C₃H₆O, was synthesized by N-alkylation of α-amino-(2-chlorophenyl)acetate with 2-thienylethyl p-toluenesulfonate, followed by reaction with (+)-camphor-10-sulfonic acid. In the crystal, the cations and anions are linked through N—H⋯O hydrogen bonds. The thiophene ring of the cation was found to be disordered over two sites, with refined occupancies of 0.798 (4) and 0.202 (4).

Related literature

For background to the antiplatelet agent clopidogrel, see: Kang et al. (2007 ▶). For the preparation of the title compound, an intermediate of clopidogrel, see: Descamps & Radisson (1992 ▶). For a database of bond lengths and angles, see: Bruno et al. (2004 ▶).

Experimental

Crystal data

C₁₅H₁₇ClNO₂S⁺·C₁₀H₁₅O₄S⁻·C₃H₆O
M _r = 600.16
Orthorhombic,
a = 12.101 (3) Å
b = 14.209 (4) Å
c = 18.325 (5) Å
V = 3150.7 (14) Å³
Z = 4
Mo Kα radiation
μ = 0.30 mm⁻¹
T = 294 K
0.26 × 0.24 × 0.20 mm

Data collection

Bruker SMART-CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.912, T _max = 0.943
18154 measured reflections
6435 independent reflections
4010 reflections with I > 2σ(I)
R _int = 0.039

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.096
S = 0.99
6435 reflections
402 parameters
70 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.18 e Å⁻³
Absolute structure: Flack (1983 ▶), 2828 Friedel pairs
Flack parameter: −0.04 (6)

Data collection: SMART (Bruker, 1997 ▶); cell refinement: SAINT (Bruker, 1997 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681004523X/bh2318sup1.cif

e-66-o3117-sup1.cif^{(27.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053681004523X/bh2318Isup2.hkl

e-66-o3117-Isup2.hkl^{(315KB, hkl)}

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—H1B⋯O3	0.93 (3)	1.82 (3)	2.729 (3)	164 (3)
N1—H1A⋯O5ⁱ	0.88 (3)	2.63 (2)	3.180 (3)	121.1 (19)
N1—H1A⋯O4ⁱ	0.88 (3)	1.99 (3)	2.856 (3)	169 (2)

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank Mr Hai-Bin Song (Nankai University) for the X-ray crystallographic determination and helpful discussions.

supplementary crystallographic information

Comment

Clopidogrel treatment is associated with a reduction in thrombotic complications in coronary stent placement, improved outcome after acute coronary syndromes, and decreased mortality in patients with coronary artery disease (Kang et al., 2007). Now, we present the crystal structure of the title compound, (I), an intermediate of Clopidogrel (Fig. 1, Table 1).

All bond lengths and angles in (I) are within normal ranges (Bruno et al., 2004). In the cation, C5 to C9, N1, O1 and O2 are almost coplanar (r.m.s. deviation 0.0363 Å and maximum deviation 0.0610 (2) Å). In the anion, the dihedral angles formed between C17 to C20 plane and C17/C20/C21 plane, C17/C20/C21 plane and C17/C20/C24/C25 plane are 54.45 (2)° and 54.47 (3)°, respectively. The crystal is stabilized by N—H···O hydrogen bonds between the cations and the anions, which link the molecules into sheets in the bc plane (Fig. 2, Table 2).

Experimental

(I) was prepared according to the method of Descamps & Radisson (1992). 12.5 g of methyl alpha-amino(2-chlorophenyl)acetate was released from its hydrochloride by reaction with 9 g of NaHCO₃ in the presence of 200 ml of CH₂Cl₂ and 65 ml of water. The resulting amine was dissolved in 65 ml of acetonitrile; 6.2 g of NaHCO₃ and 15.6 g of 2-thienylethyl-para-toluenesulfonate were then introduced; the mixture was kept at 353 K for 22 h and the volatile products were then evaporated off under reduced pressure. The residue was dissolved in 200 ml of ethyl acetate and 65 ml of water; the organic phase was separated off. After the usual treatments the aminoester was obtained and dissolved in 70 ml of acetone, then 8.7 g of (+)-10-camphorsulfonic acid was introduced. The mixture was stirred at room temperature for 12 h to get precipitate, and 11 g of camphorsulfonate was thus obtained. The camphorsulfonate was suspended in 50 ml of refluxing acetone and 25 ml of methyl ethyl ketone to obtain complete dissolution. The mixture was standing under 298 K, then white crystals were grown slowly. The crystals were washed with cold acetone, yield 6.8 g, m.p. 368 K.