1-(5-Bromo-2-chloro­phen­yl)-2,2-di­chloro-1-(4-eth­oxy­phen­yl)cyclo­propane

Shuwen Han; Yongheng Shi; Wang Yuli; Guilong Zhao; Weiren Xu

doi:10.1107/S1600536813003735

. 2013 Feb 20;69(Pt 3):o405. doi: 10.1107/S1600536813003735

1-(5-Bromo-2-chlorophenyl)-2,2-dichloro-1-(4-ethoxyphenyl)cyclopropane

Shuwen Han ^a,^b, Yongheng Shi ^a,^b, Wang Yuli ^b, Guilong Zhao ^b, Weiren Xu ^a,^b,^*

PMCID: PMC3588413 PMID: 23476586

Abstract

The asymmetric unit of the title compound, C₁₇H₁₄BrCl₃O, contains two independent molecules with different dihedral angles between the benzene rings [79.2 (1) and 72.7 (1)°]. In the crystal, weak C—H⋯π interactions link molecules related by translation along the b axis into two crystallographically independent chains.

Related literature

For background to sodium-glucose cotransporter 2 (SGLT2) inhibitors, see: Washburn (2009 ▶); Meng et al. (2008 ▶). For the crystal structures of related cyclopropane derivatives, see: DeLacy & Kennard (1972 ▶); Lauher & Ibers (1975 ▶).

Experimental

Crystal data

C₁₇H₁₄BrCl₃O
M _r = 420.54
Monoclinic,
a = 27.447 (13) Å
b = 8.886 (4) Å
c = 28.861 (14) Å
β = 98.348 (8)°
V = 6965 (6) Å³
Z = 16
Mo Kα radiation
μ = 2.82 mm⁻¹
T = 113 K
0.20 × 0.18 × 0.14 mm

Data collection

Rigaku Saturn724 CCD diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2009 ▶) T _min = 0.603, T _max = 0.694
26327 measured reflections
6143 independent reflections
4903 reflections with I > 2σ(I)
R _int = 0.104

Refinement

R[F ² > 2σ(F ²)] = 0.067
wR(F ²) = 0.180
S = 1.09
6143 reflections
399 parameters
H-atom parameters constrained
Δρ_max = 1.54 e Å⁻³
Δρ_min = −0.89 e Å⁻³

Data collection: CrystalClear (Rigaku/MSC, 2009 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; 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

Click here for additional data file.^{(28KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813003735/cv5386sup1.cif

e-69-0o405-sup1.cif^{(28KB, cif)}

Click here for additional data file.^{(300.8KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813003735/cv5386Isup2.hkl

e-69-0o405-Isup2.hkl^{(300.8KB, hkl)}

Click here for additional data file.^{(5.6KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813003735/cv5386Isup3.cml

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

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

Cg1 is the centroid of the C10–C15 ring and Cg2 is the centroid of the C27–C32 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C3—H3⋯Cg1ⁱ	0.95	2.66	3.665 (3)	161
C20—H20⋯Cg2ⁱⁱ	0.95	2.60	3.480 (9)	155

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

supplementary crystallographic information

Comment

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of anti-diabetic drugs with novel mechanism of action. The most advanced drug, dapagliflozin, has recently been approved in EU (Meng et al., 2008; Washburn, 2009). During our search for new SGLT2 inhibitors, we prepared the title compound as a key intermediate for the synthesis of a new class of cyclopropane-bearing SGLT2 inhibitors.

The asymmetric unit of the title compound, C₁₇H₁₄BrCl₃O, contains two independent molecules with different dihedral angles between the benzene rings [79.2 (1) and 72.7 (1)°]. Bond lengths are normal and in a good agreement with those reported previously for related structures (DeLacy & Kennard, 1972; Lauher & Ibers 1975). In the crystal, weak C—H···π interactions (Table 1) link the molecules related by translation along the axis b into two crystallographically independent chains.

Experimental

3.38 g (10 mmol) of 1-(5-bromo-2-chlorophenyl)-1-(4-ethoxyphenyl)ethene was dissolved in 15 ml of chloroform and stirred at room temperature, followed by addition of 3 ml of 50% aqueous NaOH and 0.5 g of benzyltriethylammonium bromide. The reaction mixture was stirred vigorously at room temperature overnight until all the starting ethene was consumed as indicated by TLC. The reaction mixture was poured into 200 ml of water and extracted with three 50-ml portions of dichloromethane. The combined extracts were washed with saturated brine, dried over anhydrous sodium sulfate and evaporated on a rotary evaporator to afford the crude product as a colorless oil, which was purified by column chromatography to yield the pure product as colorless crystals. Single crystals suitable for X-ray diffraction were obtained through slow evaporation of a solution of the pure title compound in petroleum ether.