11-{[2-(3-Fluoro­phen­yl)eth­yl](meth­yl)amino}­penta­cyclo­[5.4.0.02,6.03,10.05,9]undecan-8-one

Banister, S.D.; Clegg, J.K.; Hanani, R.; Kassiou, M.

doi:10.1107/S1600536810038523

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 10| October 2010| Page o2693

doi:10.1107/S1600536810038523

Open

access

11-{[2-(3-Fluorophenyl)ethyl](methyl)amino}pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecan-8-one

Samuel D. Banister,^a Jack K. Clegg,^a,^b Raphy Hanani ^a and Michael Kassiou ^a,^c ^*

^aSchool of Chemistry, F11, The University of Sydney, New South Wales 2006, Australia, ^bDepartment of Chemistry, University of Cambridge, Lensfield Rd, Cambridge CB2 1EW, England, and ^cBrain and Mind Research Institute, Sydney, New South Wales 2050, Australia, Discipline of Medical Radiation Sciences, The University of Sydney, New South Wales 2006, Australia
^*Correspondence e-mail: m.kassiou@chem.usyd.edu.au

(Received 5 September 2010; accepted 26 September 2010; online 30 September 2010)

In the title compound, C₂₀H₂₂FNO, the distances close to the carbonyl and amine are: N—O = 3.232 (4) Å and N—C = 2.666 (5) Å. The crystal packing is unremarkable.

Related literature

For in vitro σ-receptor affinity of trishomocubane derivatives related to the title compound, see: Nguyen et al. (1996 ); Liu et al. (1999 ). For in vivo pharmacology of related trishomocubanes, see: Liu et al. (2001 , 2007 ). For rationalization of observed structure–affinity relationships of trishomocubanes at σ-receptors using molecular modeling, see: Banister et al. (2010 ). For X-ray crystallographic studies of biologically active trishomocubanes related to the title compound, see: Hambley et al. (2000 ).

Experimental

Crystal data

C₂₀H₂₂FNO
M_r = 311.39
Monoclinic, P 2₁ /n
a = 10.5450 (18) Å
b = 10.980 (2) Å
c = 13.822 (3) Å
β = 95.214 (8)°
V = 1593.8 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 150 K
0.25 × 0.20 × 0.15 mm

Data collection

Bruker–Nonius APEXII FR591 diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1999 ) T_min = 0.684, T_max = 0.746
17270 measured reflections
2773 independent reflections
1566 reflections with I > 2σ(I)
R_int = 0.087

Refinement

R[F² > 2σ(F²)] = 0.087
wR(F²) = 0.271
S = 1.14
2773 reflections
209 parameters
H-atom parameters constrained
Δρ_max = 0.69 e Å⁻³
Δρ_min = −0.48 e Å⁻³

Data collection: APEX2 (Bruker–Nonius, 2003 ); cell refinement: SAINT (Bruker–Nonius, 2003); data reduction: SAINT and XPREP (Bruker–Nonius, 2003); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: ORTEP-3 (Farrugia, 1997 ), WinGX (Farrugia, 1999 ) and POV-RAY (Cason, 2002 ); software used to prepare material for publication: enCIFer (Allen et al., 2004 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810038523/rk2233sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536810038523/rk2233Isup2.hkl

checkCIF report

Comment top

Trishomocubanes have been shown to have in vitro σ-receptor affinity and selectivity [Nguyen et al., (1996); Liu et al., (1999)] and a number of their crystal structures have been reported [Hambley et al., (2000)]. Several trishomocubane derivatives synthesized in our laboratory were reported to possess anti-cocaine activity in vivo [Liu et al., (2001), (Liu et al., (2007)]. The importance of the nature ofthe hemiaminal bridge of N-(2-(3-fluorophenyl)ethyl)-4-azahexacyclo [5.4.1.0^2,6.0^3,10.0^5,9.0^8,11]dodecan-3-ol I *(Fig. 1) to σ-receptor binding was demonstrated by the reduced affinity, and off-target activity, of the corresponding hemiaminal ether, N-(2-(3-fluorophenyl)ethyl)-3-amino-4-oxapentacyclo [5.4.1.0^2,6.0^3,10.0^5,9.0^8,11]dodecane II [Banister et al., (2010)] (Fig. 1). In our ongoing efforts to elucidate the nature of σ-receptor binding we have synthesized the title compound III (Fig. 1) as a methyl homologue of I, representing a "locked" form of the non-transannular, aminoketone tautomer of the latter. A molecular and crystal structures were obtained to unambiguously confirm the structure of III (Fig. 2), and to identify key interatomic distances, for use in modeling studies. Important distances are those close to the carbonyl and amine, including: N1–O1 = 3.232 (4)Å; N1–C18 = 2.666 (5)Å; O1–C9 = 3.943 (5)Å; C9–C18 = 3.574 (6)Å.

Related literature top

For in vitro σ-receptor affinity of trishomocubane derivatives related to the title compound, see: Nguyen et al. (1996); Liu et al. (1999). For in vivo pharmacology of related trishomocubanes, see: Liu et al. (2001, 2007). For rationalization of observed structure–affinity relationships of trishomocubanes at σ-receptors using molecular modeling, see: Banister et al. (2010). For X-ray crystallographic studies of biologically active trishomocubanes related to the title compound, see: Hambley et al. (2000).

Experimental top

A solution of N-(2-(3-fluorophenyl)ethyl)-4-azahexacyclo [5.4.1.0^2,6.0^3,10.0^5,9.0^8,11]dodecan-3-ol (942 mg, 3.17 mmol) and 37% aqueous formaldehyde (285 µL, 3.80 mmol, 1.2 equiv.) in ClCH₂CH₂Cl (30 ml) was treated with NaBH(OAc)₃ (3.359 g, 15.85 mmol, 5 equiv.) and the mixture stirred for 18 h. The reaction was quenched with 1 M aqueous NaOH (30 ml), and the layers separated. The aqueous layer was extracted with CH₂Cl₂ (3 × 15 ml) and the combined organic layers were washed with brine (25 ml), dried (Na₂SO₄) and the solvent evaporated. Purification was achieved using column chromatography on silica eluting with CHCl₃-MeOH-conc. aq. NH₄OH (90:9:1) to give N-(2-(3-fluorophenyl)ethyl)-N-methyl-11-aminopentacyclo [5.4.0.0^2,6.0^3,10.0^5,9]undecan-8-one III as colourless crystals (902 mg, 91%): m. pt. 363-364.5 K; R_f 0.43 (90:9:1 v/v/v CHCl₃:MeOH: conc. aq. NH₄OH); IR (thin film) cm^-1; 2970, 2861, 1721 (C═O), 1582, 1484, 1426, 1343, 1229, 1141, 1059, 981, 939, 906, 791; ¹H NMR (400 MHz, CDCl₃); δ 7.25-7.19 (1H, m, ArH), 6.93 (1H, d, J = 7.9 Hz, ArH), 6.89-6.85 (2H, m, ArH), 3.02-2.97 (1H, m, CH), 2.87-2.67 (7H, m, CH), 2.66-2.62 (2H, m, CH), 2.50 (1H, t, J = 4.2 Hz, CH), 2.47-2.43 (1H, m, CH), 2.35-2.31 (1H, m, CH), 2.30 (3H, s, CH₃), 1.86 (1H, d, J = 10.8 Hz, CHCH₂CH), 1.48 (1H, d, J = 10.8 Hz, CHCH₂CH); ¹³C NMR (100.6 MHz, CDCl₃); δ 213.1 (C═O), 163.0 (3'-C, ¹J_C–F = 245.3 Hz), 143.4 (1'-C, ³J_C–F = 7.4 Hz), 129.9 (5'-C, ³J_C–F = 8.3 Hz), 124.5 (6'-C, ⁴J_C–F = 2.6 Hz), 115.6 (2'-C, ²J_C–F = 20.8 Hz), 112.9 (4'-C, ²J_C–F = 21.1 Hz), 64.6 (CH), 57.1 (CH₂), 51.6 (CH), 50.1 (CH), 46.4 (CH), 42.1 (CH), 41.6 (CH), 41.4 (CH), 40.8 (CH), 40.2 (CH), 38.5 (CH₂), 37.2 (CH), 31.7 (CH₂); m/z (+ESI) 312.13 ([M + H]⁺, 100); Anal. (C₂₀H₂₂NOF): calc, C 77.14, H 7.12, N 4.50; found, C 76.90, H 7.19, N 4.55. Crystals suitable for X-ray diffraction were grown by the slow evaporation of a hexane solution.

Computing details top

Data collection: APEX2 (Bruker–Nonius, 2003); cell refinement: SAINT (Bruker–Nonius, 2003); data reduction: SAINT and XPREP (Bruker–Nonius, 2003); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997), WinGX (Farrugia, 1999) and POV-RAY (Cason, 2002); software used to prepare material for publication: enCIFer (Allen et al., 2004).

Figures top

	Fig. 1. Chemical structures of I, II and III.
	Fig. 2. 221ORTEP representation of III with atom numbering scheme. Displacement ellipsoids are shown at 50% probability level. H atoms are presented as a small spheres of arbitrary radius.

11-{[2-(3-Fluorophenyl)ethyl](methyl)amino}pentacyclo [5.4.0.0^2,6.0^3,10.0^5,9]undecan-8-one top

Crystal data top

C₂₀H₂₂FNO	F(000) = 664
M_r = 311.39	D_x = 1.298 Mg m⁻³
Monoclinic, P2₁/n	Melting point: 363.5 K
Hall symbol: -P 2yn	Mo Kα radiation, λ = 0.71073 Å
a = 10.5450 (18) Å	Cell parameters from 2297 reflections
b = 10.980 (2) Å	θ = 2.7–23.1°
c = 13.822 (3) Å	µ = 0.09 mm⁻¹
β = 95.214 (8)°	T = 150 K
V = 1593.8 (5) Å³	Block, colourless
Z = 4	0.25 × 0.20 × 0.15 mm

Data collection top

Bruker–Nonius APEXII FR591 diffractometer	2773 independent reflections
Radiation source: rotating anode	1566 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.087
ω and ϕ scans	θ_max = 25.0°, θ_min = 3.0°
Absorption correction: multi-scan (SADABS; Sheldrick, 1999)	h = −12→12
T_min = 0.684, T_max = 0.746	k = −13→12
17270 measured reflections	l = −16→16

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)] = 0.087	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.271	H-atom parameters constrained
S = 1.14	w = 1/[σ²(F_o²) + (0.1415P)² + 0.2766P] where P = (F_o² + 2F_c²)/3
2773 reflections	(Δ/σ)_max < 0.001
209 parameters	Δρ_max = 0.69 e Å⁻³
0 restraints	Δρ_min = −0.48 e Å⁻³

Crystal data top

C₂₀H₂₂FNO	V = 1593.8 (5) Å³
M_r = 311.39	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 10.5450 (18) Å	µ = 0.09 mm⁻¹
b = 10.980 (2) Å	T = 150 K
c = 13.822 (3) Å	0.25 × 0.20 × 0.15 mm
β = 95.214 (8)°

Data collection top

Bruker–Nonius APEXII FR591 diffractometer	2773 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1999)	1566 reflections with I > 2σ(I)
T_min = 0.684, T_max = 0.746	R_int = 0.087
17270 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.087	0 restraints
wR(F²) = 0.271	H-atom parameters constrained
S = 1.14	Δρ_max = 0.69 e Å⁻³
2773 reflections	Δρ_min = −0.48 e Å⁻³
209 parameters

Special details top

Experimental. The crystal was coated in Exxon Paratone N hydrocarbon oil and mounted on a thin mohair fibre attached to a copper pin. Upon mounting on the diffractometer, the crystal was quenched to 150 K under a cold nitrogen gas stream supplied by an Oxford Cryosystems Cryostream and data were collected at this temperature.

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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
C1	0.5938 (5)	0.3609 (4)	0.6172 (5)	0.0588 (17)
C2	0.5803 (4)	0.2626 (4)	0.6825 (3)	0.0399 (11)
H2	0.5450	0.2744	0.7426	0.048*
C3	0.6209 (3)	0.1482 (3)	0.6545 (3)	0.0250 (9)
C4	0.6703 (4)	0.1374 (4)	0.5656 (3)	0.0382 (11)
H4	0.6988	0.0598	0.5462	0.046*
C5	0.6797 (5)	0.2343 (6)	0.5047 (4)	0.0609 (16)
H5	0.7123	0.2220	0.4436	0.073*
C6	0.6442 (6)	0.3449 (6)	0.5291 (5)	0.0680 (18)
H6	0.6532	0.4120	0.4869	0.082*
C7	0.6123 (5)	0.0379 (4)	0.7189 (3)	0.0503 (13)
H7A	0.6156	0.0645	0.7875	0.060*
H7B	0.6865	−0.0156	0.7121	0.060*
C8	0.4885 (4)	−0.0351 (4)	0.6931 (3)	0.0304 (10)
H8A	0.4162	0.0131	0.7137	0.036*
H8B	0.4758	−0.0436	0.6216	0.036*
C9	0.5715 (4)	−0.2420 (4)	0.6958 (4)	0.0490 (13)
H9A	0.6587	−0.2249	0.7233	0.074*
H9B	0.5661	−0.2326	0.6250	0.074*
H9C	0.5486	−0.3256	0.7119	0.074*
C10	0.4948 (4)	−0.1550 (4)	0.8423 (3)	0.0348 (11)
H10	0.5795	−0.1212	0.8675	0.042*
C11	0.3871 (4)	−0.0811 (4)	0.8822 (3)	0.0408 (12)
H11	0.3956	0.0094	0.8774	0.049*
C12	0.3700 (5)	−0.1303 (4)	0.9854 (4)	0.0506 (13)
H12	0.3736	−0.0702	1.0400	0.061*
C13	0.4537 (4)	−0.2406 (5)	0.9980 (3)	0.0502 (14)
H13	0.5343	−0.2286	1.0409	0.060*
C14	0.4724 (4)	−0.2781 (4)	0.8898 (3)	0.0479 (13)
H14	0.5445	−0.3364	0.8851	0.057*
C15	0.3636 (5)	−0.3402 (5)	1.0322 (4)	0.0542 (14)
H15A	0.4011	−0.4229	1.0328	0.065*
H15B	0.3314	−0.3216	1.0957	0.065*
C16	0.2635 (4)	−0.3182 (5)	0.9450 (3)	0.0470 (13)
H16	0.1859	−0.3705	0.9451	0.056*
C17	0.3392 (4)	−0.3332 (4)	0.8509 (4)	0.0469 (13)
H17	0.3429	−0.4186	0.8262	0.056*
C18	0.2639 (4)	−0.2484 (4)	0.7847 (3)	0.0379 (11)
C19	0.2540 (4)	−0.1331 (5)	0.8456 (3)	0.0429 (12)
H19	0.1893	−0.0720	0.8196	0.052*
C20	0.2372 (4)	−0.1834 (4)	0.9485 (3)	0.0435 (12)
H20	0.1614	−0.1557	0.9812	0.052*
N1	0.4837 (3)	−0.1570 (3)	0.7364 (2)	0.0259 (8)
O1	0.2010 (3)	−0.2730 (3)	0.70829 (19)	0.0431 (9)
F1	0.5547 (4)	0.4710 (3)	0.6455 (4)	0.128 (2)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.035 (3)	0.016 (2)	0.119 (5)	0.004 (2)	−0.030 (3)	−0.007 (3)
C2	0.023 (2)	0.053 (3)	0.043 (3)	−0.007 (2)	−0.0052 (18)	−0.016 (2)
C3	0.028 (2)	0.026 (2)	0.020 (2)	−0.0055 (18)	−0.0039 (16)	0.0031 (16)
C4	0.036 (2)	0.045 (3)	0.033 (3)	0.001 (2)	0.0019 (19)	−0.007 (2)
C5	0.044 (3)	0.104 (5)	0.034 (3)	−0.023 (3)	−0.001 (2)	0.017 (3)
C6	0.056 (4)	0.070 (4)	0.074 (4)	−0.032 (3)	−0.019 (3)	0.038 (4)
C7	0.053 (3)	0.047 (3)	0.046 (3)	−0.028 (2)	−0.021 (2)	0.021 (2)
C8	0.028 (2)	0.036 (2)	0.026 (2)	−0.0048 (19)	−0.0042 (17)	0.0024 (18)
C9	0.039 (3)	0.044 (3)	0.063 (3)	0.007 (2)	0.001 (2)	−0.011 (2)
C10	0.031 (2)	0.041 (3)	0.030 (2)	−0.017 (2)	−0.0098 (18)	0.0099 (19)
C11	0.046 (3)	0.050 (3)	0.027 (2)	−0.023 (2)	0.009 (2)	−0.006 (2)
C12	0.066 (3)	0.043 (3)	0.040 (3)	−0.015 (3)	−0.009 (2)	−0.005 (2)
C13	0.031 (2)	0.090 (4)	0.028 (2)	−0.011 (3)	−0.0097 (19)	0.012 (2)
C14	0.040 (3)	0.044 (3)	0.056 (3)	−0.014 (2)	−0.015 (2)	0.020 (2)
C15	0.057 (3)	0.059 (3)	0.045 (3)	−0.008 (3)	−0.006 (2)	0.018 (2)
C16	0.046 (3)	0.070 (4)	0.023 (2)	−0.028 (3)	−0.003 (2)	0.006 (2)
C17	0.042 (3)	0.037 (3)	0.058 (3)	−0.016 (2)	−0.013 (2)	0.010 (2)
C18	0.033 (2)	0.051 (3)	0.028 (2)	−0.019 (2)	−0.0031 (19)	0.008 (2)
C19	0.039 (3)	0.058 (3)	0.033 (3)	−0.006 (2)	0.005 (2)	0.001 (2)
C20	0.039 (3)	0.060 (3)	0.032 (3)	−0.002 (2)	0.006 (2)	0.008 (2)
N1	0.0248 (17)	0.0248 (18)	0.0278 (19)	−0.0006 (15)	0.0002 (13)	0.0012 (14)
O1	0.0350 (16)	0.070 (2)	0.0232 (16)	−0.0208 (16)	−0.0058 (13)	0.0024 (14)
F1	0.088 (3)	0.038 (2)	0.246 (6)	0.0133 (19)	−0.048 (3)	−0.037 (2)

Geometric parameters (Å, º) top

C1—F1	1.347 (6)	C10—H10	1.0000
C1—C6	1.384 (9)	C11—C12	1.551 (7)
C1—C2	1.422 (7)	C11—C19	1.557 (6)
C2—C3	1.393 (6)	C11—H11	1.0000
C2—H2	0.9500	C12—C13	1.499 (7)
C3—C4	1.382 (6)	C12—C20	1.560 (7)
C3—C7	1.511 (6)	C12—H12	1.0000
C4—C5	1.366 (7)	C13—C15	1.551 (7)
C4—H4	0.9500	C13—C14	1.581 (7)
C5—C6	1.323 (8)	C13—H13	1.0000
C5—H5	0.9500	C14—C17	1.579 (6)
C6—H6	0.9500	C14—H14	1.0000
C7—C8	1.546 (6)	C15—C16	1.546 (6)
C7—H7A	0.9900	C15—H15A	0.9900
C7—H7B	0.9900	C15—H15B	0.9900
C8—N1	1.469 (5)	C16—C20	1.508 (7)
C8—H8A	0.9900	C16—C17	1.595 (7)
C8—H8B	0.9900	C16—H16	1.0000
C9—N1	1.463 (5)	C17—C18	1.484 (6)
C9—H9A	0.9800	C17—H17	1.0000
C9—H9B	0.9800	C18—O1	1.225 (5)
C9—H9C	0.9800	C18—C19	1.529 (7)
C10—N1	1.458 (5)	C19—C20	1.550 (6)
C10—C14	1.531 (6)	C19—H19	1.0000
C10—C11	1.538 (6)	C20—H20	1.0000

F1—C1—C6	121.4 (6)	C13—C12—H12	117.7
F1—C1—C2	116.5 (6)	C11—C12—H12	117.7
C6—C1—C2	122.0 (5)	C20—C12—H12	117.7
C3—C2—C1	117.2 (4)	C12—C13—C15	103.6 (4)
C3—C2—H2	121.4	C12—C13—C14	102.9 (3)
C1—C2—H2	121.4	C15—C13—C14	103.7 (4)
C4—C3—C2	118.3 (4)	C12—C13—H13	115.0
C4—C3—C7	120.2 (4)	C15—C13—H13	115.0
C2—C3—C7	121.5 (4)	C14—C13—H13	115.0
C5—C4—C3	122.4 (5)	C10—C14—C17	111.0 (3)
C5—C4—H4	118.8	C10—C14—C13	102.3 (4)
C3—C4—H4	118.8	C17—C14—C13	103.8 (4)
C6—C5—C4	121.3 (5)	C10—C14—H14	113.0
C6—C5—H5	119.3	C17—C14—H14	113.0
C4—C5—H5	119.3	C13—C14—H14	113.0
C5—C6—C1	118.7 (5)	C16—C15—C13	92.6 (3)
C5—C6—H6	120.6	C16—C15—H15A	113.2
C1—C6—H6	120.6	C13—C15—H15A	113.2
C3—C7—C8	112.0 (3)	C16—C15—H15B	113.2
C3—C7—H7A	109.2	C13—C15—H15B	113.2
C8—C7—H7A	109.2	H15A—C15—H15B	110.5
C3—C7—H7B	109.2	C20—C16—C15	104.1 (4)
C8—C7—H7B	109.2	C20—C16—C17	103.6 (4)
H7A—C7—H7B	107.9	C15—C16—C17	105.2 (4)
N1—C8—C7	116.0 (3)	C20—C16—H16	114.2
N1—C8—H8A	108.3	C15—C16—H16	114.2
C7—C8—H8A	108.3	C17—C16—H16	114.2
N1—C8—H8B	108.3	C18—C17—C14	112.3 (3)
C7—C8—H8B	108.3	C18—C17—C16	99.1 (4)
H8A—C8—H8B	107.4	C14—C17—C16	100.2 (4)
N1—C9—H9A	109.5	C18—C17—H17	114.4
N1—C9—H9B	109.5	C14—C17—H17	114.4
H9A—C9—H9B	109.5	C16—C17—H17	114.4
N1—C9—H9C	109.5	O1—C18—C17	127.6 (4)
H9A—C9—H9C	109.5	O1—C18—C19	126.7 (4)
H9B—C9—H9C	109.5	C17—C18—C19	103.9 (4)
N1—C10—C14	114.6 (3)	C18—C19—C20	103.2 (4)
N1—C10—C11	112.0 (3)	C18—C19—C11	112.2 (4)
C14—C10—C11	99.4 (3)	C20—C19—C11	90.4 (3)
N1—C10—H10	110.1	C18—C19—H19	115.9
C14—C10—H10	110.1	C20—C19—H19	115.9
C11—C10—H10	110.1	C11—C19—H19	115.9
C10—C11—C12	107.3 (4)	C16—C20—C19	106.5 (4)
C10—C11—C19	111.3 (3)	C16—C20—C12	102.4 (4)
C12—C11—C19	89.7 (3)	C19—C20—C12	89.6 (3)
C10—C11—H11	115.2	C16—C20—H20	118.0
C12—C11—H11	115.2	C19—C20—H20	118.0
C19—C11—H11	115.2	C12—C20—H20	118.0
C13—C12—C11	105.8 (4)	C10—N1—C9	113.5 (3)
C13—C12—C20	103.8 (4)	C10—N1—C8	113.1 (3)
C11—C12—C20	90.3 (3)	C9—N1—C8	112.3 (3)

F1—C1—C2—C3	−179.7 (4)	C13—C14—C17—C18	104.4 (4)
C6—C1—C2—C3	0.5 (6)	C10—C14—C17—C16	−109.2 (4)
C1—C2—C3—C4	−0.6 (6)	C13—C14—C17—C16	0.0 (4)
C1—C2—C3—C7	179.2 (4)	C20—C16—C17—C18	−41.0 (4)
C2—C3—C4—C5	−0.4 (6)	C15—C16—C17—C18	−150.0 (4)
C7—C3—C4—C5	179.8 (4)	C20—C16—C17—C14	73.7 (4)
C3—C4—C5—C6	1.6 (7)	C15—C16—C17—C14	−35.3 (5)
C4—C5—C6—C1	−1.6 (8)	C14—C17—C18—O1	137.7 (5)
F1—C1—C6—C5	−179.2 (5)	C16—C17—C18—O1	−117.2 (5)
C2—C1—C6—C5	0.6 (8)	C14—C17—C18—C19	−56.7 (5)
C4—C3—C7—C8	−85.8 (5)	C16—C17—C18—C19	48.4 (4)
C2—C3—C7—C8	94.4 (5)	O1—C18—C19—C20	127.7 (4)
C3—C7—C8—N1	167.1 (4)	C17—C18—C19—C20	−38.0 (4)
N1—C10—C11—C12	154.8 (3)	O1—C18—C19—C11	−136.4 (4)
C14—C10—C11—C12	33.3 (4)	C17—C18—C19—C11	58.0 (4)
N1—C10—C11—C19	58.2 (4)	C10—C11—C19—C18	3.5 (5)
C14—C10—C11—C19	−63.3 (4)	C12—C11—C19—C18	−105.0 (4)
C10—C11—C12—C13	−7.4 (5)	C10—C11—C19—C20	108.1 (4)
C19—C11—C12—C13	104.9 (4)	C12—C11—C19—C20	−0.5 (4)
C10—C11—C12—C20	−111.8 (4)	C15—C16—C20—C19	128.1 (4)
C19—C11—C12—C20	0.5 (4)	C17—C16—C20—C19	18.3 (4)
C11—C12—C13—C15	−128.9 (4)	C15—C16—C20—C12	34.8 (4)
C20—C12—C13—C15	−34.7 (4)	C17—C16—C20—C12	−75.0 (4)
C11—C12—C13—C14	−21.1 (4)	C18—C19—C20—C16	10.6 (4)
C20—C12—C13—C14	73.1 (4)	C11—C19—C20—C16	−102.3 (4)
N1—C10—C14—C17	−55.1 (5)	C18—C19—C20—C12	113.4 (4)
C11—C10—C14—C17	64.4 (5)	C11—C19—C20—C12	0.5 (4)
N1—C10—C14—C13	−165.3 (3)	C13—C12—C20—C16	0.0 (4)
C11—C10—C14—C13	−45.8 (4)	C11—C12—C20—C16	106.3 (4)
C12—C13—C14—C10	42.8 (4)	C13—C12—C20—C19	−106.8 (4)
C15—C13—C14—C10	150.5 (4)	C11—C12—C20—C19	−0.5 (4)
C12—C13—C14—C17	−72.8 (4)	C14—C10—N1—C9	−58.3 (5)
C15—C13—C14—C17	34.9 (5)	C11—C10—N1—C9	−170.6 (3)
C12—C13—C15—C16	53.3 (4)	C14—C10—N1—C8	172.2 (3)
C14—C13—C15—C16	−53.9 (4)	C11—C10—N1—C8	59.9 (4)
C13—C15—C16—C20	−53.6 (4)	C7—C8—N1—C10	61.1 (5)
C13—C15—C16—C17	55.0 (4)	C7—C8—N1—C9	−69.0 (5)
C10—C14—C17—C18	−4.9 (6)

Experimental details

Crystal data
Chemical formula	C₂₀H₂₂FNO
M_r	311.39
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	150
a, b, c (Å)	10.5450 (18), 10.980 (2), 13.822 (3)
β (°)	95.214 (8)
V (Å³)	1593.8 (5)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.25 × 0.20 × 0.15

Data collection
Diffractometer	Bruker–Nonius APEXII FR591 diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1999)
T_min, T_max	0.684, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	17270, 2773, 1566
R_int	0.087
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.087, 0.271, 1.14
No. of reflections	2773
No. of parameters	209
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.69, −0.48

Computer programs: APEX2 (Bruker–Nonius, 2003), SAINT (Bruker–Nonius, 2003), SAINT and XPREP (Bruker–Nonius, 2003), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997), WinGX (Farrugia, 1999) and POV-RAY (Cason, 2002), enCIFer (Allen et al., 2004).

Acknowledgements

We gratefully acknowledge the Australian Research Council for support. JKC acknowledges the Marie Curie IIF scheme of the 7th EU Framework Program.

References

Allen, F. H., Johnson, O., Shields, G. P., Smith, B. R. & Towler, M. (2004). J. Appl. Cryst. 37, 335–338. Web of Science CrossRef CAS IUCr Journals Google Scholar
Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115–119. Web of Science CrossRef CAS IUCr Journals Google Scholar
Banister, S. D., Moussa, I. A., Jordan, M. J. T., Coster, M. J. & Kassiou, M. (2010). Bioorg. Med. Chem. Lett. 20, 145–148. Web of Science CrossRef PubMed CAS Google Scholar
Bruker–Nonius (2003). APEX2, SAINT and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cason, C. J. (2002). POV-RAY. Hallam Oaks Pty Ltd, Williamstown, Victoria, Australia. Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Hambley, T. W., Knott, R., Kassiou, M. & Christie, M. J. (2000). Aust. J. Chem. 53, 899–904. Web of Science CSD CrossRef CAS Google Scholar
Liu, X., Banister, S. D., Christie, M. J., Banati, R., Meikle, S., Coster, M. J. & Kassiou, M. (2007). Eur. J. Pharmacol. 555, 37–42. Web of Science CrossRef PubMed CAS Google Scholar
Liu, X., Kassiou, M. & Christie, M. J. (1999). Aust. J. Chem. 52, 653–656. Web of Science CrossRef CAS Google Scholar
Liu, X., Nuwayhid, S., Christie, M. J., Kassiou, M. & Werling, L. L. (2001). Eur. J. Pharmacol. 422, 39–45. Web of Science CrossRef PubMed CAS Google Scholar
Nguyen, V. H., Kassiou, M., Johnston, G. A. & Christie, M. J. (1996). Eur. J. Pharmacol. 311, 233–240. CrossRef CAS PubMed Web of Science Google Scholar
Sheldrick, G. M. (1999). SADABS. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.