4-(3-Fluoro-4-nitro­phen­yl)morpholin-3-one

Chang-Jiang Huang; Jiang Wu; Zhi-Qiang Cai; Jing Yuan

doi:10.1107/S1600536811019738

. 2011 May 28;67(Pt 6):o1549. doi: 10.1107/S1600536811019738

4-(3-Fluoro-4-nitrophenyl)morpholin-3-one

Chang-Jiang Huang ^a,^*, Jiang Wu ^b, Zhi-Qiang Cai ^a, Jing Yuan ^a

PMCID: PMC3120424 PMID: 21754908

Abstract

In the title compound, C₁₀H₉FN₂O₄, the dihedral angle between the benzene ring and the nitro group plane is 11.29 (3)°. The morpholinone ring adopts a twist-chair conformation. In the crystal, molecules are linked by intermolecular C—H⋯O hydrogen bonds into a chain along the a-axis direction.

Related literature

The title compound is an intermediate in the preparation of derivatives of the factor Xa inhibitor rivaroxaban (systematic name (S)-5-chloro-N-{[2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]oxazolidin-5-yl]methyl}thiophene-2-carboxamide). For the bioactivity and applications of rivaroxaban, see: Pinto et al. (2010 ▶); Haas (2008 ▶); Squizzato et al. (2009 ▶); Samama & Gerotziafas (2010 ▶); Van Huis et al. (2009 ▶). For the synthesis of other derivatives with morpholone, see: Van Huis et al. (2009 ▶); Zbinden et al. (2009 ▶).

Experimental

Crystal data

C₁₀H₉FN₂O₄
M _r = 240.19
Triclinic,
a = 6.6408 (7) Å
b = 7.3788 (10) Å
c = 10.8546 (14) Å
α = 73.30 (3)°
β = 75.39 (3)°
γ = 74.30 (3)°
V = 481.60 (14) Å³
Z = 2
Mo Kα radiation
μ = 0.14 mm⁻¹
T = 113 K
0.22 × 0.20 × 0.10 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: ψ scan (CrystalClear; Rigaku/MSC, 2009 ▶) T _min = 0.970, T _max = 0.986
6470 measured reflections
2569 independent reflections
1734 reflections with I > 2σ(I)
R _int = 0.041

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.104
S = 0.97
2569 reflections
154 parameters
H-atom parameters constrained
Δρ_max = 0.56 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: RAPID-AUTO (Rigaku, 1998 ▶); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; 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: CrystalStructure (Rigaku/MSC, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811019738/kp2328sup1.cif

e-67-o1549-sup1.cif^{(16.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811019738/kp2328Isup2.hkl

e-67-o1549-Isup2.hkl^{(126.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811019738/kp2328Isup3.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
C6—H6⋯O2ⁱ	0.95	2.39	3.2635 (16)	153
C2—H2B⋯O3ⁱⁱ	0.99	2.50	3.3244 (19)	140
C1—H1B⋯O4ⁱⁱⁱ	0.99	2.57	3.515 (2)	161

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

Acknowledgments

The authors thank the State Key Laboratory of Elemento-organic Chemistry, Nankai University, for the data collection.

supplementary crystallographic information

Comment

Rivaroxaban is an oral, direct factor Xa inhibitor for the prevention and treatment of arterial and venous thrombosis (Pinto et al., 2010; Haas, 2008; Squizzato et al., 2009).

The title compound (Fig. 1) is important intermediate in the preparation of derivatives of Rivaroxaban. Some derivatives of Rivaroxaban have been reported for having high affinity for human FXa (Squizzato et al., 2009; Samama et al., 2010; Van Huis et al., 2009). Herein, the synthesis and the crystal structure of the title compound are reported.

In the title compound, C₁₀H₉F₁N₂O₄, the dihedral angle between benzene ring and the plane of nitro group is 11.29 (3)°. The morpholone ring adopts a twist-chair conformation. In the crystal packing molecules are linked by intermolecular C—H···O hydrogen bonds into a chain (Table 1).

Experimental

Potassium carbonate (6.73 g, 0.0488 mol) was added to a suspension of 2-(2-chloroethoxy)-N-(3-fluoro-4-nitrophenyl)acetamide (9.00 g, 0.0325 mol) in acetonitrile (200 mL).The reaction mixture was stirred at 385 K for 5 h. The mixture was evaporated in vacuo. Water was added.The reaction mixture was filtered, washed with water, and dried to obtain yellow solid (7.19 g).Colourless single crystals suitable for X-ray diffraction were obtained by recrystallisation from ethanol and ethyl acetate.