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

Huang, C.-J.; Wu, J.; Cai, Z.-Q.; Yuan, J.

doi:10.1107/S1600536811019738

organic compounds

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ISSN: 2056-9890

Volume 67| Part 6| June 2011| Page o1549

doi:10.1107/S1600536811019738

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

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

^aTianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, People's Republic of China, and ^bTianjin Institute of Pharmaceutical Research, Tianjin 300193, People's Republic of China
^*Correspondence e-mail: czq0601@gmail.com

(Received 16 May 2011; accepted 24 May 2011; online 28 May 2011)

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, $[P \overline 1]$
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[F² > 2σ(F²)] = 0.039
wR(F²) = 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

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
Symmetry codes: (i) x+1, y, z; (ii) x, y, z+1; (iii) -x+2, -y+1, -z.

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).

Supporting information

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

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

Supporting information file. DOI: 10.1107/S1600536811019738/kp2328Isup3.cml

checkCIF report

Comment top

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).

Related literature top

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 et al. (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 top

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.

Computing details top

Data collection: RAPID-AUTO (Rigaku, 1998); cell refinement: RAPID-AUTO (Rigaku, 1998); data reduction: RAPID-AUTO (Rigaku, 1998); 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).

Figures top

Fig. 1. The structure of C₁₀H₉F₁N₂O₄ with all non-H atom-labelling scheme and displacement ellipsoids drawn at the 50% probability level.

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

Crystal data top

C₁₀H₉FN₂O₄	Z = 2
M_r = 240.19	F(000) = 248
Triclinic, P1	D_x = 1.656 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.6408 (7) Å	Cell parameters from 1909 reflections
b = 7.3788 (10) Å	θ = 2.0–31.1°
c = 10.8546 (14) Å	µ = 0.14 mm⁻¹
α = 73.30 (3)°	T = 113 K
β = 75.39 (3)°	Prism, colourless
γ = 74.30 (3)°	0.22 × 0.20 × 0.10 mm
V = 481.60 (14) Å³

Data collection top

Rigaku Saturn CCD area-detector diffractometer	2569 independent reflections
Radiation source: rotating anode	1734 reflections with I > 2σ(I)
Multilayer monochromator	R_int = 0.041
Detector resolution: 14.63 pixels mm^-1	θ_max = 29.1°, θ_min = 2.0°
ω and ϕ scans	h = −9→9
Absorption correction: ψ scan (CrystalClear; Rigaku/MSC, 2009)	k = −10→9
T_min = 0.970, T_max = 0.986	l = −14→14
6470 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.104	H-atom parameters constrained
S = 0.97	w = 1/[σ²(F_o²) + (0.0502P)²] where P = (F_o² + 2F_c²)/3
2569 reflections	(Δ/σ)_max < 0.001
154 parameters	Δρ_max = 0.56 e Å⁻³
0 restraints	Δρ_min = −0.25 e Å⁻³

Crystal data top

C₁₀H₉FN₂O₄	γ = 74.30 (3)°
M_r = 240.19	V = 481.60 (14) Å³
Triclinic, P1	Z = 2
a = 6.6408 (7) Å	Mo Kα radiation
b = 7.3788 (10) Å	µ = 0.14 mm⁻¹
c = 10.8546 (14) Å	T = 113 K
α = 73.30 (3)°	0.22 × 0.20 × 0.10 mm
β = 75.39 (3)°

Data collection top

Rigaku Saturn CCD area-detector diffractometer	2569 independent reflections
Absorption correction: ψ scan (CrystalClear; Rigaku/MSC, 2009)	1734 reflections with I > 2σ(I)
T_min = 0.970, T_max = 0.986	R_int = 0.041
6470 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.039	0 restraints
wR(F²) = 0.104	H-atom parameters constrained
S = 0.97	Δρ_max = 0.56 e Å⁻³
2569 reflections	Δρ_min = −0.25 e Å⁻³
154 parameters

Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
F1	0.38071 (13)	0.73231 (13)	−0.24062 (8)	0.0292 (2)
O1	0.23003 (15)	0.94560 (12)	0.40672 (8)	0.0192 (2)
O2	0.04787 (15)	0.82852 (15)	0.16307 (9)	0.0262 (2)
O3	0.74637 (16)	0.59970 (13)	−0.37865 (9)	0.0241 (2)
O4	1.03428 (15)	0.62270 (13)	−0.32888 (9)	0.0234 (2)
N1	0.39251 (16)	0.79057 (14)	0.18692 (10)	0.0139 (2)
N2	0.84043 (18)	0.63168 (15)	−0.30564 (10)	0.0165 (2)
C1	0.5325 (2)	0.77071 (18)	0.27977 (12)	0.0161 (3)
H1A	0.6152	0.8739	0.2456	0.019*
H1B	0.6347	0.6443	0.2855	0.019*
C2	0.4068 (2)	0.78419 (19)	0.41571 (12)	0.0201 (3)
H2A	0.3550	0.6634	0.4599	0.024*
H2B	0.5001	0.7996	0.4685	0.024*
C3	0.0821 (2)	0.90024 (19)	0.35316 (12)	0.0183 (3)
H3A	−0.0349	1.0155	0.3382	0.022*
H3B	0.0196	0.7956	0.4183	0.022*
C4	0.1736 (2)	0.83638 (18)	0.22515 (12)	0.0164 (3)
C5	0.4968 (2)	0.75696 (16)	0.06139 (12)	0.0132 (3)
C6	0.7205 (2)	0.71941 (17)	0.03016 (12)	0.0160 (3)
H6	0.7988	0.7192	0.0924	0.019*
C7	0.8283 (2)	0.68282 (17)	−0.09000 (12)	0.0161 (3)
H7	0.9795	0.6591	−0.1095	0.019*
C8	0.7182 (2)	0.68025 (17)	−0.18264 (12)	0.0143 (3)
C9	0.4967 (2)	0.72366 (18)	−0.15317 (12)	0.0158 (3)
C10	0.3858 (2)	0.76283 (17)	−0.03458 (12)	0.0160 (3)
H10	0.2345	0.7938	−0.0178	0.019*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0201 (5)	0.0495 (5)	0.0226 (4)	−0.0038 (4)	−0.0079 (4)	−0.0158 (4)
O1	0.0176 (5)	0.0226 (5)	0.0198 (5)	−0.0014 (4)	−0.0046 (4)	−0.0102 (4)
O2	0.0134 (5)	0.0476 (6)	0.0235 (5)	−0.0093 (5)	−0.0009 (4)	−0.0173 (5)
O3	0.0289 (6)	0.0285 (5)	0.0192 (5)	−0.0068 (4)	−0.0067 (4)	−0.0099 (4)
O4	0.0162 (5)	0.0297 (5)	0.0214 (5)	−0.0027 (4)	0.0012 (4)	−0.0078 (4)
N1	0.0125 (5)	0.0173 (5)	0.0125 (5)	−0.0031 (4)	−0.0020 (4)	−0.0049 (4)
N2	0.0192 (6)	0.0143 (5)	0.0148 (5)	−0.0029 (5)	−0.0020 (5)	−0.0028 (4)
C1	0.0135 (6)	0.0200 (7)	0.0159 (6)	−0.0013 (5)	−0.0055 (5)	−0.0056 (5)
C2	0.0196 (7)	0.0234 (7)	0.0158 (6)	0.0000 (6)	−0.0051 (5)	−0.0053 (5)
C3	0.0162 (7)	0.0218 (7)	0.0173 (6)	−0.0031 (5)	−0.0026 (5)	−0.0063 (5)
C4	0.0147 (7)	0.0177 (7)	0.0163 (6)	−0.0045 (5)	−0.0007 (5)	−0.0044 (5)
C5	0.0153 (6)	0.0117 (6)	0.0129 (6)	−0.0041 (5)	−0.0021 (5)	−0.0029 (5)
C6	0.0154 (7)	0.0182 (7)	0.0162 (6)	−0.0045 (5)	−0.0048 (5)	−0.0043 (5)
C7	0.0133 (6)	0.0181 (7)	0.0175 (6)	−0.0041 (5)	−0.0027 (5)	−0.0047 (5)
C8	0.0161 (7)	0.0134 (6)	0.0132 (6)	−0.0033 (5)	−0.0014 (5)	−0.0036 (5)
C9	0.0166 (7)	0.0180 (7)	0.0153 (6)	−0.0042 (5)	−0.0071 (5)	−0.0036 (5)
C10	0.0111 (6)	0.0188 (7)	0.0183 (6)	−0.0018 (5)	−0.0035 (5)	−0.0051 (5)

Geometric parameters (Å, º) top

F1—C9	1.3438 (13)	C2—H2B	0.9900
O1—C3	1.4118 (14)	C3—C4	1.5223 (18)
O1—C2	1.4286 (16)	C3—H3A	0.9900
O2—C4	1.2193 (14)	C3—H3B	0.9900
O3—N2	1.2292 (13)	C5—C10	1.4050 (16)
O4—N2	1.2349 (13)	C5—C6	1.4061 (18)
N1—C4	1.3823 (16)	C6—C7	1.3831 (17)
N1—C5	1.4223 (16)	C6—H6	0.9500
N1—C1	1.4885 (15)	C7—C8	1.3910 (16)
N2—C8	1.4630 (16)	C7—H7	0.9500
C1—C2	1.5171 (18)	C8—C9	1.3912 (18)
C1—H1A	0.9900	C9—C10	1.3795 (18)
C1—H1B	0.9900	C10—H10	0.9500
C2—H2A	0.9900

C3—O1—C2	107.55 (9)	C4—C3—H3B	108.5
C4—N1—C5	123.48 (11)	H3A—C3—H3B	107.5
C4—N1—C1	120.11 (10)	O2—C4—N1	124.24 (12)
C5—N1—C1	116.39 (10)	O2—C4—C3	117.50 (12)
O3—N2—O4	123.82 (11)	N1—C4—C3	118.25 (11)
O3—N2—C8	118.74 (11)	C10—C5—C6	118.08 (11)
O4—N2—C8	117.43 (10)	C10—C5—N1	122.88 (11)
N1—C1—C2	112.26 (10)	C6—C5—N1	119.03 (11)
N1—C1—H1A	109.2	C7—C6—C5	120.88 (12)
C2—C1—H1A	109.2	C7—C6—H6	119.6
N1—C1—H1B	109.2	C5—C6—H6	119.6
C2—C1—H1B	109.2	C6—C7—C8	120.88 (12)
H1A—C1—H1B	107.9	C6—C7—H7	119.6
O1—C2—C1	109.95 (10)	C8—C7—H7	119.6
O1—C2—H2A	109.7	C7—C8—C9	118.10 (12)
C1—C2—H2A	109.7	C7—C8—N2	118.60 (11)
O1—C2—H2B	109.7	C9—C8—N2	123.31 (11)
C1—C2—H2B	109.7	F1—C9—C10	116.88 (12)
H2A—C2—H2B	108.2	F1—C9—C8	121.12 (12)
O1—C3—C4	114.95 (11)	C10—C9—C8	121.99 (12)
O1—C3—H3A	108.5	C9—C10—C5	119.97 (12)
C4—C3—H3A	108.5	C9—C10—H10	120.0
O1—C3—H3B	108.5	C5—C10—H10	120.0

C4—N1—C1—C2	6.24 (15)	N1—C5—C6—C7	178.93 (10)
C5—N1—C1—C2	−172.77 (10)	C5—C6—C7—C8	−0.66 (19)
C3—O1—C2—C1	70.39 (13)	C6—C7—C8—C9	2.70 (19)
N1—C1—C2—O1	−46.84 (14)	C6—C7—C8—N2	−177.12 (11)
C2—O1—C3—C4	−52.83 (13)	O3—N2—C8—C7	168.82 (11)
C5—N1—C4—O2	9.8 (2)	O4—N2—C8—C7	−10.19 (16)
C1—N1—C4—O2	−169.11 (11)	O3—N2—C8—C9	−10.99 (18)
C5—N1—C4—C3	−170.40 (11)	O4—N2—C8—C9	170.00 (11)
C1—N1—C4—C3	10.66 (17)	C7—C8—C9—F1	176.97 (10)
O1—C3—C4—O2	−167.37 (11)	N2—C8—C9—F1	−3.22 (19)
O1—C3—C4—N1	12.84 (16)	C7—C8—C9—C10	−1.95 (19)
C4—N1—C5—C10	−1.57 (18)	N2—C8—C9—C10	177.87 (11)
C1—N1—C5—C10	177.41 (11)	F1—C9—C10—C5	−179.83 (10)
C4—N1—C5—C6	177.30 (11)	C8—C9—C10—C5	−0.87 (19)
C1—N1—C5—C6	−3.73 (16)	C6—C5—C10—C9	2.90 (18)
C10—C5—C6—C7	−2.16 (18)	N1—C5—C10—C9	−178.23 (11)

Hydrogen-bond geometry (Å, º) top

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

Symmetry codes: (i) x+1, y, z; (ii) x, y, z+1; (iii) −x+2, −y+1, −z.

Experimental details

Crystal data
Chemical formula	C₁₀H₉FN₂O₄
M_r	240.19
Crystal system, space group	Triclinic, P1
Temperature (K)	113
a, b, c (Å)	6.6408 (7), 7.3788 (10), 10.8546 (14)
α, β, γ (°)	73.30 (3), 75.39 (3), 74.30 (3)
V (Å³)	481.60 (14)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.14
Crystal size (mm)	0.22 × 0.20 × 0.10

Data collection
Diffractometer	Rigaku Saturn CCD area-detector diffractometer
Absorption correction	ψ scan (CrystalClear; Rigaku/MSC, 2009)
T_min, T_max	0.970, 0.986
No. of measured, independent and observed [I > 2σ(I)] reflections	6470, 2569, 1734
R_int	0.041
(sin θ/λ)_max (Å⁻¹)	0.685

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.039, 0.104, 0.97
No. of reflections	2569
No. of parameters	154
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.56, −0.25

Computer programs: RAPID-AUTO (Rigaku, 1998), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008), CrystalStructure (Rigaku/MSC, 2009).

Hydrogen-bond geometry (Å, º) top

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

Symmetry codes: (i) x+1, y, z; (ii) x, y, z+1; (iii) −x+2, −y+1, −z.

Acknowledgements

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

References

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