(1R*,5S*)-8-(2-Fluoro-4-nitro­phen­yl)-8-aza­bicyclo­[3.2.1]octan-3-one

Yang, T.; Yang, J.; Li, Z.; Luo, Y.

doi:10.1107/S1600536811047350

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 67| Part 12| December 2011| Page o3297

https://doi.org/10.1107/S1600536811047350

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(1R,5S)-8-(2-Fluoro-4-nitrophenyl)-8-azabicyclo[3.2.1]octan-3-one

Tao Yang,^a Jianzhong Yang,^a Zicheng Li ^b and Youfu Luo ^a ^*

^aState Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China, and ^bDepartment of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, People's Republic of China
^*Correspondence e-mail: luo_youfu@scu.edu.cn

(Received 2 August 2011; accepted 9 November 2011; online 12 November 2011)

In the title compound, C₁₃H₁₃FN₂O₃, the fused piperidine ring is in a chair conformation. The fused pyrrolidine ring shows an envelope conformation with the N atom displaced by 0.661 (3) Å out of the plane formed by the four C atoms of the pyrrolidine ring. The dihedral angle between this plane and the plane formed by the four attached C atoms of the piperidine ring (not including the carbonyl C atom) is 67.63 (10)°. The F atom is disordered and was refined using a split model with an occupancy ratio of 0.910 (3): 0.080 (3).

Related literature

For a related structure, see Yang et al. (2008 ).

Experimental

Crystal data

C₁₃H₁₃FN₂O₃
M_r = 264.25
Monoclinic, P 2₁ /c
a = 7.2030 (3) Å
b = 11.3097 (4) Å
c = 14.8372 (6) Å
β = 97.391 (4)°
V = 1198.65 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 293 K
0.38 × 0.35 × 0.30 mm

Data collection

Agilent Xcalibur Eos diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010 ) T_min = 0.997, T_max = 1.0
4706 measured reflections
2109 independent reflections
1482 reflections with I > 2σ(I)
R_int = 0.016

Refinement

R[F² > 2σ(F²)] = 0.044
wR(F²) = 0.113
S = 1.02
2109 reflections
183 parameters
H-atom parameters constrained
Δρ_max = 0.14 e Å⁻³
Δρ_min = −0.12 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2010); 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: OLEX2 (Dolomanov et al., 2009 ); software used to prepare material for publication: OLEX2.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536811047350/nc2245sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536811047350/nc2245Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536811047350/nc2245Isup3.cml

checkCIF report

Comment top

The title compound is one important synthetic intermediates in our efforts to synthesize oxazolidinone derivatives. To identify< this compound its single crystal structure was determined by single crystal X-ray diffraction.

The dihedral angle between the benzene ring and the plane built up of C7, C8, C10 and C11 of the piperidine ring is 86.59 (9)° while the angle between the plane defined by this four C atoms and the plane formed by the four C atoms of the pyrrolidine ring is 67.63 (10)°. The fused piperidine ring is in a chair conformation with the N atom and one C atom displaced by 0.8433 (26) Å and -0.3798 (33) Å out of the mean plane defined by the other four atoms. The fused pyrrolidine ring adopts an envelope conformation with the N atom deviating by 0.661 (3) Å.

Related literature top

For a related structure, see Yang et al. (2008).

Experimental top

A solution of 1,2-difluoro-4-nitrobenzene (2.5 g, 15.7 mmol), nortropinone hydrochloride (3.8 g, 23.6 mmol) and anhydrous potassium carbonate (4.3 g,31.4 mmol) in DMF (75 mL) was stirred at 100°C for 2 h. Water (300 ml) was added and precipitation was formed. (1R, 5S)-8-(2-fluoro-4-nitrophenyl)-8- azabicyclo[3.2.1]octan-3-one was collected by filtration and recrystallized from ethylacetate.Crystals suitable for X-ray analysis were obtained by slow evaporation from a solution of the title compound in acetone.

Structure description top

For a related structure, see Yang et al. (2008).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2010); cell refinement: CrysAlis PRO (Agilent, 2010); data reduction: CrysAlis PRO (Agilent, 2010); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top

Fig. 1. The molecular structure of the title compound, with labeling and displacement ellipsoids drawn at the 30% probability level. The disorder is shown as full and open bonds.

(1R*,5S*)-8-(2-Fluoro-4-nitrophenyl)-8-azabicyclo[3.2.1]octan-3- one top

Crystal data top

C₁₃H₁₃FN₂O₃	F(000) = 552
M_r = 264.25	D_x = 1.464 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.7107 Å
Hall symbol: -P 2ybc	Cell parameters from 1673 reflections
a = 7.2030 (3) Å	θ = 3.0–28.9°
b = 11.3097 (4) Å	µ = 0.12 mm⁻¹
c = 14.8372 (6) Å	T = 293 K
β = 97.391 (4)°	Block, yellow
V = 1198.65 (8) Å³	0.38 × 0.35 × 0.30 mm
Z = 4

Data collection top

Agilent Xcalibur Eos diffractometer	2109 independent reflections
Radiation source: fine-focus sealed tube	1482 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.016
Detector resolution: 16.0874 pixels mm^-1	θ_max = 25.0°, θ_min = 3.3°
ω scans	h = −8→8
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010)	k = −8→13
T_min = 0.997, T_max = 1.0	l = −17→14
4706 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.044	H-atom parameters constrained
wR(F²) = 0.113	w = 1/[σ²(F_o²) + (0.0452P)² + 0.1579P] where P = (F_o² + 2F_c²)/3
S = 1.02	(Δ/σ)_max < 0.001
2109 reflections	Δρ_max = 0.14 e Å⁻³
183 parameters	Δρ_min = −0.12 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0037 (11)

Crystal data top

C₁₃H₁₃FN₂O₃	V = 1198.65 (8) Å³
M_r = 264.25	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 7.2030 (3) Å	µ = 0.12 mm⁻¹
b = 11.3097 (4) Å	T = 293 K
c = 14.8372 (6) Å	0.38 × 0.35 × 0.30 mm
β = 97.391 (4)°

Data collection top

Agilent Xcalibur Eos diffractometer	2109 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010)	1482 reflections with I > 2σ(I)
T_min = 0.997, T_max = 1.0	R_int = 0.016
4706 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.044	0 restraints
wR(F²) = 0.113	H-atom parameters constrained
S = 1.02	Δρ_max = 0.14 e Å⁻³
2109 reflections	Δρ_min = −0.12 e Å⁻³
183 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	Occ. (<1)
F1	0.6635 (2)	0.70834 (11)	0.61012 (10)	0.0924 (6)	0.910 (3)
F1'	0.716 (2)	0.2944 (9)	0.6621 (9)	0.080 (6)	0.090 (3)
O1	1.1163 (2)	0.57062 (17)	0.92502 (11)	0.0972 (6)
O2	0.7844 (3)	0.54056 (17)	0.32301 (12)	0.0929 (6)
O3	0.8052 (3)	0.35184 (18)	0.34414 (12)	0.1019 (6)
N1	0.6650 (2)	0.51844 (13)	0.73584 (11)	0.0530 (4)
N2	0.7860 (2)	0.4527 (2)	0.37182 (13)	0.0706 (6)
C1	0.7027 (3)	0.59691 (16)	0.58549 (15)	0.0568 (5)
H1	0.6815	0.6733	0.6051	0.068*	0.090 (3)
C2	0.7289 (3)	0.58145 (18)	0.49751 (15)	0.0592 (6)
H2	0.7253	0.6459	0.4584	0.071*
C3	0.7608 (3)	0.46959 (18)	0.46658 (14)	0.0534 (5)
C4	0.7681 (3)	0.37456 (18)	0.52508 (14)	0.0583 (6)
H4	0.7901	0.2988	0.5044	0.070*
C5	0.7427 (3)	0.39274 (16)	0.61379 (14)	0.0537 (5)
H5	0.7504	0.3280	0.6528	0.064*	0.910 (3)
C6	0.7055 (2)	0.50442 (15)	0.64893 (13)	0.0469 (5)
C7	0.6776 (3)	0.63004 (17)	0.78822 (14)	0.0608 (6)
H7	0.6162	0.6951	0.7523	0.073*
C8	0.8836 (3)	0.65642 (18)	0.81689 (15)	0.0659 (6)
H8A	0.9432	0.6734	0.7633	0.079*
H8B	0.8948	0.7262	0.8552	0.079*
C9	0.9831 (3)	0.5552 (2)	0.86761 (14)	0.0648 (6)
C10	0.9161 (3)	0.43248 (18)	0.84129 (14)	0.0627 (6)
H10B	0.9423	0.3808	0.8936	0.075*
H10A	0.9857	0.4031	0.7942	0.075*
C11	0.7064 (3)	0.42723 (17)	0.80686 (13)	0.0568 (5)
H11	0.6703	0.3485	0.7832	0.068*
C12	0.5736 (3)	0.5997 (2)	0.86856 (17)	0.0799 (7)
H12B	0.6325	0.6376	0.9236	0.096*
H12A	0.4443	0.6254	0.8571	0.096*
C13	0.5847 (3)	0.4658 (2)	0.87766 (16)	0.0720 (7)
H13B	0.6410	0.4432	0.9381	0.086*
H13A	0.4612	0.4306	0.8658	0.086*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.1396 (15)	0.0391 (8)	0.1023 (11)	0.0162 (8)	0.0297 (10)	0.0065 (7)
F1'	0.137 (14)	0.028 (7)	0.074 (9)	−0.001 (7)	0.017 (8)	0.013 (6)
O1	0.0642 (11)	0.1378 (16)	0.0858 (12)	−0.0305 (10)	−0.0049 (9)	−0.0118 (11)
O2	0.0934 (14)	0.1075 (14)	0.0781 (11)	−0.0261 (11)	0.0124 (9)	0.0127 (10)
O3	0.1195 (17)	0.0967 (14)	0.0929 (13)	−0.0086 (12)	0.0269 (11)	−0.0254 (11)
N1	0.0507 (10)	0.0397 (9)	0.0676 (11)	−0.0017 (7)	0.0040 (8)	−0.0014 (8)
N2	0.0501 (11)	0.0876 (16)	0.0732 (14)	−0.0159 (11)	0.0048 (9)	−0.0051 (12)
C1	0.0535 (13)	0.0351 (11)	0.0812 (15)	0.0038 (9)	0.0066 (11)	0.0018 (10)
C2	0.0477 (12)	0.0523 (13)	0.0765 (15)	−0.0031 (10)	0.0037 (10)	0.0138 (11)
C3	0.0349 (11)	0.0593 (13)	0.0644 (13)	−0.0056 (9)	0.0004 (9)	−0.0025 (10)
C4	0.0481 (12)	0.0488 (12)	0.0749 (15)	0.0017 (9)	−0.0036 (10)	−0.0074 (11)
C5	0.0478 (12)	0.0424 (11)	0.0676 (13)	0.0024 (9)	−0.0050 (10)	0.0017 (10)
C6	0.0330 (10)	0.0399 (11)	0.0657 (13)	0.0002 (8)	−0.0019 (9)	−0.0013 (9)
C7	0.0551 (13)	0.0461 (12)	0.0833 (15)	0.0002 (10)	0.0166 (11)	−0.0080 (10)
C8	0.0647 (15)	0.0551 (13)	0.0810 (15)	−0.0168 (11)	0.0210 (11)	−0.0181 (11)
C9	0.0432 (12)	0.0883 (17)	0.0649 (14)	−0.0143 (12)	0.0142 (10)	−0.0139 (12)
C10	0.0553 (13)	0.0660 (14)	0.0661 (13)	0.0060 (11)	0.0048 (10)	0.0038 (10)
C11	0.0557 (13)	0.0466 (11)	0.0664 (13)	−0.0072 (10)	0.0019 (10)	0.0023 (10)
C12	0.0624 (15)	0.0776 (17)	0.1054 (19)	−0.0054 (13)	0.0326 (13)	−0.0145 (14)
C13	0.0540 (14)	0.0802 (17)	0.0827 (16)	−0.0116 (12)	0.0121 (11)	0.0040 (13)

Geometric parameters (Å, º) top

F1—C1	1.352 (2)	C5—C6	1.405 (3)
F1'—C5	1.350 (11)	C7—H7	0.9800
O1—C9	1.211 (2)	C7—C8	1.519 (3)
O2—N2	1.229 (2)	C7—C12	1.526 (3)
O3—N2	1.226 (2)	C8—H8A	0.9700
N1—C6	1.368 (2)	C8—H8B	0.9700
N1—C7	1.479 (2)	C8—C9	1.501 (3)
N1—C11	1.477 (2)	C9—C10	1.504 (3)
N2—C3	1.453 (3)	C10—H10B	0.9700
C1—H1	0.9300	C10—H10A	0.9700
C1—C2	1.354 (3)	C10—C11	1.532 (3)
C1—C6	1.405 (3)	C11—H11	0.9800
C2—H2	0.9300	C11—C13	1.516 (3)
C2—C3	1.375 (3)	C12—H12B	0.9700
C3—C4	1.378 (3)	C12—H12A	0.9700
C4—H4	0.9300	C12—C13	1.522 (3)
C4—C5	1.368 (3)	C13—H13B	0.9700
C5—H5	0.9300	C13—H13A	0.9700

F1—C1—C2	116.15 (18)	C6—C1—H1	118.1
F1—C1—C6	119.9 (2)	C6—C5—H5	118.4
F1'—C5—C4	115.6 (6)	C7—C8—H8A	109.2
F1'—C5—H5	12.4	C7—C8—H8B	109.2
F1'—C5—C6	119.7 (6)	C7—C12—H12B	110.6
O1—C9—C8	121.8 (2)	C7—C12—H12A	110.6
O1—C9—C10	120.9 (2)	C8—C7—H7	111.2
O2—N2—C3	118.1 (2)	C8—C7—C12	112.66 (19)
O3—N2—O2	123.2 (2)	C8—C9—C10	117.21 (18)
O3—N2—C3	118.7 (2)	H8A—C8—H8B	107.9
N1—C6—C1	123.97 (17)	C9—C8—C7	112.12 (18)
N1—C6—C5	121.87 (17)	C9—C8—H8A	109.2
N1—C7—H7	111.2	C9—C8—H8B	109.2
N1—C7—C8	107.84 (16)	C9—C10—H10B	109.0
N1—C7—C12	102.44 (17)	C9—C10—H10A	109.0
N1—C11—C10	108.09 (16)	C9—C10—C11	113.06 (17)
N1—C11—H11	111.1	C10—C11—H11	111.1
N1—C11—C13	102.23 (16)	H10B—C10—H10A	107.8
C1—C2—H2	120.3	C11—N1—C7	103.18 (15)
C1—C2—C3	119.37 (19)	C11—C10—H10B	109.0
C2—C1—H1	118.1	C11—C10—H10A	109.0
C2—C1—C6	123.89 (18)	C11—C13—C12	104.67 (18)
C2—C3—N2	119.4 (2)	C11—C13—H13B	110.8
C2—C3—C4	120.1 (2)	C11—C13—H13A	110.8
C3—C2—H2	120.3	C12—C7—H7	111.2
C3—C4—H4	120.3	C12—C13—H13B	110.8
C4—C3—N2	120.5 (2)	C12—C13—H13A	110.8
C4—C5—H5	118.4	H12B—C12—H12A	108.8
C4—C5—C6	123.22 (19)	C13—C11—C10	113.00 (17)
C5—C4—C3	119.33 (19)	C13—C11—H11	111.1
C5—C4—H4	120.3	C13—C12—C7	105.51 (18)
C5—C6—C1	114.05 (19)	C13—C12—H12B	110.6
C6—N1—C7	126.04 (16)	C13—C12—H12A	110.6
C6—N1—C11	122.93 (16)	H13B—C13—H13A	108.9

F1—C1—C2—C3	−177.08 (17)	C6—N1—C7—C8	−74.0 (2)
F1—C1—C6—N1	2.1 (3)	C6—N1—C7—C12	167.00 (18)
F1—C1—C6—C5	178.26 (17)	C6—N1—C11—C10	77.6 (2)
F1'—C5—C6—N1	8.4 (8)	C6—N1—C11—C13	−162.92 (17)
F1'—C5—C6—C1	−167.9 (8)	C6—C1—C2—C3	−0.1 (3)
O1—C9—C10—C11	152.0 (2)	C7—N1—C6—C1	−23.0 (3)
O2—N2—C3—C2	2.6 (3)	C7—N1—C6—C5	161.09 (17)
O2—N2—C3—C4	−177.66 (18)	C7—N1—C11—C10	−73.0 (2)
O3—N2—C3—C2	−176.46 (19)	C7—N1—C11—C13	46.42 (19)
O3—N2—C3—C4	3.3 (3)	C7—C8—C9—O1	−150.3 (2)
N1—C7—C8—C9	−54.7 (2)	C7—C8—C9—C10	32.5 (3)
N1—C7—C12—C13	23.7 (2)	C7—C12—C13—C11	4.1 (2)
N1—C11—C13—C12	−30.4 (2)	C8—C7—C12—C13	−91.9 (2)
N2—C3—C4—C5	−179.57 (16)	C8—C9—C10—C11	−30.7 (3)
C1—C2—C3—N2	179.04 (17)	C9—C10—C11—N1	50.9 (2)
C1—C2—C3—C4	−0.7 (3)	C9—C10—C11—C13	−61.5 (2)
C2—C1—C6—N1	−174.79 (18)	C10—C11—C13—C12	85.5 (2)
C2—C1—C6—C5	1.4 (3)	C11—N1—C6—C1	−166.83 (16)
C2—C3—C4—C5	0.2 (3)	C11—N1—C6—C5	17.3 (3)
C3—C4—C5—F1'	167.7 (8)	C11—N1—C7—C8	75.5 (2)
C3—C4—C5—C6	1.2 (3)	C11—N1—C7—C12	−43.6 (2)
C4—C5—C6—N1	174.33 (17)	C12—C7—C8—C9	57.6 (2)
C4—C5—C6—C1	−2.0 (3)

Experimental details

Crystal data
Chemical formula	C₁₃H₁₃FN₂O₃
M_r	264.25
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	7.2030 (3), 11.3097 (4), 14.8372 (6)
β (°)	97.391 (4)
V (Å³)	1198.65 (8)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.12
Crystal size (mm)	0.38 × 0.35 × 0.30

Data collection
Diffractometer	Agilent Xcalibur Eos
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2010)
T_min, T_max	0.997, 1.0
No. of measured, independent and observed [I > 2σ(I)] reflections	4706, 2109, 1482
R_int	0.016
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.113, 1.02
No. of reflections	2109
No. of parameters	183
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.14, −0.12

Computer programs: CrysAlis PRO (Agilent, 2010), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009).

Acknowledgements

We thank the Analytical and Testing Center of Sichuan University for the X-ray measurements.

References

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