l-Nebiviololinium chloride dihydrate

Tuchalski, G.; Hänsicke, A.; Reck, G.; Emmerling, F.

doi:10.1107/S1600536807061831

organic compounds

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ISSN: 2056-9890

Volume 64| Part 1| January 2008| Page o54

https://doi.org/10.1107/S1600536807061831

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L-Nebiviololinium chloride dihydrate

Gisbert Tuchalski,^a Andre Hänsicke,^a Günther Reck ^b and Franziska Emmerling ^b ^*

^aBerlin-Chemie AG, Glienicker Weg 125, D-12489 Berlin, Germany, and ^bBundesanstalt für Materialforschung und prüfung, Abteilung Richard-Willstätter-Strasse 11, D-12489 Berlin-Adlershof, Germany
^*Correspondence e-mail: franziska.emmerling@bam.de

(Received 9 November 2007; accepted 21 November 2007; online 6 December 2007)

The hydrochloride salt of chiral L-nebivolol {systematic name: (+)−(R,S,S,S)-bis[2-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-hydroxyethyl]ammonium chloride dihydrate}, C₂₂H₂₆F₂NO₄⁺·Cl⁻·2H₂O, was obtained by chiral liquid chromatography as a dihydrate. The pyran rings adopt half-chair conformations. Hydrogen bonds between the cation, anions and water molecules contribute to the formation of layers parallel to the ac plane.

Related literature

For related literature, see: Cini et al. (1990 ); van Lommen et al. (1990 ); Peeters et al. (1993 ); Tuchalski et al. (2006 ).

Experimental

Crystal data

C₂₂H₂₆F₂NO₄⁺·Cl⁻·2H₂O
M_r = 477.92
Orthorhombic, P 2₁ 2₁ 2₁
a = 4.8026 (4) Å
b = 14.5781 (12) Å
c = 33.261 (3) Å
V = 2328.7 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 291 (2) K
0.60 × 0.12 × 0.09 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ) T_min = 0.865, T_max = 0.981
26222 measured reflections
3401 independent reflections
2857 reflections with I > 2σ(I)
R_int = 0.054

Refinement

R[F² > 2σ(F²)] = 0.041
wR(F²) = 0.113
S = 1.05
3401 reflections
301 parameters
6 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.24 e Å⁻³
Absolute structure: Flack (1983 ), 608 Friedel pairs
Flack parameter: −0.04 (12)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1Wⁱ	0.90	2.12	2.794 (3)	131
N1—H1⋯O4ⁱⁱ	0.90	2.37	3.056 (4)	133
N1—H2⋯O4′ⁱⁱⁱ	0.90	2.19	3.061 (4)	162
O4—H9⋯Cl1ⁱ	0.82	2.67	3.142 (2)	118
O4′—H10⋯O2Wⁱⁱ	0.82	2.04	2.701 (4)	137
O1W—H1B⋯Cl1	0.89 (4)	2.47 (4)	3.242 (2)	146 (4)
O1W—H2B⋯N1^iv	0.88 (3)	2.47 (4)	2.794 (3)	102 (3)
O2W—H1A⋯Cl1	0.89 (4)	2.29 (4)	3.175 (3)	175 (3)
O2W—H2A⋯Cl1ⁱⁱⁱ	0.88 (4)	2.37 (4)	3.242 (3)	171 (3)
C2′—H4⋯O6′	0.97	2.26	2.708 (4)	107
C2—H5⋯O6	0.97	2.35	2.738 (4)	103
C2—H6⋯O6ⁱⁱ	0.97	2.49	3.457 (4)	172
C14′—H26⋯F1^v	0.93	2.34	3.213 (5)	156
Symmetry codes: (i) $[-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) x+1, y, z; (iii) x-1, y, z; (iv) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (v) x+2, y+1, z.

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ); software used to prepare material for publication: SHELXTL (Bruker, 2001).

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536807061831/hb2656sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536807061831/hb2656Isup2.hkl

checkCIF report

Comment top

L-Nebivolol is one enantiomer of the active pharmaceutical ingredient DL-nebivolol. DL-Nebivolol is a β-blocker of the third generation exhibiting a unique activity profile (van Lommen, et al., 1990). Here we report the title compound, (I), the hydrochloride salt of L-nebivolol, obtained by chiral liquid chromatography.

The overall shape of the cation in (I) is strongly influenced by the conformation of the bridging C—C—N—C—C chain between the two benzopyran moieties. This conformation is stabilized by two intramolecular N—H···O hydrogen bonds, depicted in Figure 1. Two non-classical C—H···O intramolecular hydrogen bonds align the torsion angles C2—C3—C5—O6 and C2'-C3'-C5'-O6' in a synclinal (sc) arrangement. The length of the bridging chain defined by the distance between the carbon atoms C5 and C5' amounts to 7.434 (2) Å. O6 and O6' are in cis-position. The average C—N, C—C and C—O distances in the title compound (Fig. 1) are in good agreement with those in other nebivolol derivatives (Peeters et al., 1993; Tuchalski et al., 2006).

Figure 2 shows the packing in (I). Like in the other nebivolol isomers the molecular packing of l-nebivolol is directed by classical intermolecular hydrogen bonds. Nine unique hydrogen bonds between nitrogen and hydroxyl groups, nitrogen and water molecules, hydroxyl groups and water molecules, hydroxyl groups and chlorine as well as between water and chlorine can be observed (Table 1). Together, these result in layers propagating in (010).

Related literature top

For related literature, see: Cini et al. (1990); van Lommen et al. (1990); Peeters et al. (1993); Tuchalski et al. (2006).

Experimental top

The title compound was synthesized by a subsequent ring-opening addition reaction (Cini et al., 1990) of two different oxiran isomers with benzylamine leading to the individual benzyl-nebivolol isomers endowed with 4 chiral centers. The L-nebivolol isomer was isolated after hydrogenation and preparative chiral chromatography as its corresponding hydrochloride.

Colourless needles of (I) were grown by solvent evaporation from ethanol/ethyl acetate (1:1 v/v) at room temperature. NMR data: ¹H NMR (DMSO-d₆), δ(p.p.m.): 1.70 (1H, m); 1.77 (1H, m); 1.93 (1H, m); 2.11 (1H, m); 2.79 (4H, m); 3.05 (1H, m); 3.17 (1H, m); 3.22 (1H, m); 3.33 (1H, m); 3.89 (1H, m); 3.99 (1H, m); 3.99 (1H, m); 4.09 (1H, m); 5.75 (1H, d); 5.94 (1H, d); 6.76 (2H, dd); 6.91 (2H, m); 6.94 (2H, m); 8.63 (2H, broad) ¹³C NMR (DMSO -d₆) δ(p.p.m.): 22.1; 22.3; 23.4; 24.0; 49.4; 49.8; 67.3; 67.4; 76.7; 77.0; 113.6 (23.0); 113.6 (23.1); 115.2 (22.5); 115.3 (22.5); 117.3 (8.1); 117.3 (8.1); 123.6 (7.7); 123.7 (7.8); 150.0 (1.4); 150.4 (1.6); 155.8 (235.5); 155.9 (235.5); [αl]²⁹_D= - 20.5° (c = 1, THF/water = 4/1) chiral LC: 99.9 area-%

Structure description top

For related literature, see: Cini et al. (1990); van Lommen et al. (1990); Peeters et al. (1993); Tuchalski et al. (2006).

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: SHELXTL (Bruker, 2001).

Figures top

	Fig. 1. View of the molecular structure of (I) with 50% probability displacement ellipsoids for the non-hydrogen atoms.
	Fig. 2. View of the layers array of (I), formed via hydrogen-bonding interactions (indicated by green lines).

(+)-(R,S,S,S)-bis[2-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-\ hydroxyethyl]ammonium chloride dihydrate top

Crystal data top

C₂₂H₂₆F₂NO₄⁺·Cl⁻·2H₂O	F(000) = 1008
M_r = 477.92	D_x = 1.363 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71069 Å
Hall symbol: P 2ac 2ab	Cell parameters from 120 reflections
a = 4.8026 (4) Å	θ = 1.2–25.4°
b = 14.5781 (12) Å	µ = 0.22 mm⁻¹
c = 33.261 (3) Å	T = 291 K
V = 2328.7 (3) Å³	Needle, colourless
Z = 4	0.60 × 0.12 × 0.09 mm

Data collection top

APEX CCD area-detector diffractometer	3401 independent reflections
Radiation source: fine-focus sealed tube	2857 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.054
ω–scan	θ_max = 26.4°, θ_min = 1.2°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −6→6
T_min = 0.865, T_max = 0.981	k = −18→18
26222 measured reflections	l = −41→41

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)] = 0.041	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.113	w = 1/[σ²(F_o²) + (0.0545P)² + 0.978P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max = 0.004
3401 reflections	Δρ_max = 0.33 e Å⁻³
301 parameters	Δρ_min = −0.24 e Å⁻³
6 restraints	Absolute structure: Flack (1983), xx Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.04 (12)

Crystal data top

C₂₂H₂₆F₂NO₄⁺·Cl⁻·2H₂O	V = 2328.7 (3) Å³
M_r = 477.92	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 4.8026 (4) Å	µ = 0.22 mm⁻¹
b = 14.5781 (12) Å	T = 291 K
c = 33.261 (3) Å	0.60 × 0.12 × 0.09 mm

Data collection top

APEX CCD area-detector diffractometer	3401 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2001)	2857 reflections with I > 2σ(I)
T_min = 0.865, T_max = 0.981	R_int = 0.054
26222 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.113	Δρ_max = 0.33 e Å⁻³
S = 1.05	Δρ_min = −0.24 e Å⁻³
3401 reflections	Absolute structure: Flack (1983), xx Friedel pairs
301 parameters	Absolute structure parameter: −0.04 (12)
6 restraints

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
Cl1	0.7060 (2)	0.96561 (9)	0.28493 (3)	0.0826 (4)
O1W	0.2063 (8)	1.0846 (2)	0.24528 (8)	0.0899 (10)
H1A	0.348 (7)	0.866 (3)	0.2722 (19)	0.135*
H1B	0.348 (8)	1.075 (3)	0.2618 (13)	0.135*
O2W	0.2154 (7)	0.8243 (2)	0.26894 (9)	0.0772 (8)
H2A	0.064 (6)	0.858 (3)	0.2719 (18)	0.116*
H2B	0.191 (10)	1.0312 (17)	0.2332 (13)	0.116*
N1	0.7326 (6)	0.57169 (17)	0.33807 (7)	0.0461 (7)
H1	0.8475	0.5622	0.3171	0.069*
H2	0.5829	0.6026	0.3290	0.069*
C2'	0.8776 (7)	0.6276 (2)	0.36873 (9)	0.0435 (8)
H3	1.0288	0.5918	0.3800	0.052*
H4	0.7484	0.6414	0.3903	0.052*
C2	0.6415 (7)	0.4814 (2)	0.35470 (9)	0.0397 (8)
H5	0.5196	0.4920	0.3775	0.048*
H6	0.8035	0.4483	0.3643	0.048*
C3	0.4905 (7)	0.4230 (2)	0.32411 (9)	0.0390 (8)
H7	0.6169	0.4092	0.3018	0.058*
C3'	0.9940 (7)	0.7165 (2)	0.35241 (9)	0.0403 (8)
H8	0.8498	0.7478	0.3367	0.048*
O4	0.2600 (5)	0.47447 (14)	0.30934 (6)	0.0449 (5)
H9	0.1744	0.4437	0.2928	0.067*
O4'	1.2211 (5)	0.69428 (15)	0.32678 (6)	0.0508 (6)
H10	1.2871	0.7415	0.3174	0.076*
C5	0.3984 (7)	0.3337 (2)	0.34381 (9)	0.0403 (8)
H11	0.5645	0.3008	0.3530	0.060*
C5'	1.0904 (7)	0.7793 (2)	0.38644 (9)	0.0390 (8)
H12	1.2551	0.7521	0.3991	0.047*
O6	0.2381 (5)	0.36036 (13)	0.37856 (6)	0.0455 (6)
O6'	0.8676 (5)	0.78023 (15)	0.41512 (6)	0.0473 (6)
C7	0.0810 (7)	0.2942 (2)	0.39725 (9)	0.0421 (8)
C7'	0.8967 (7)	0.8404 (2)	0.44712 (9)	0.0411 (8)
C8	0.0283 (7)	0.2085 (2)	0.37968 (11)	0.0457 (9)
C8'	1.0804 (7)	0.9139 (2)	0.44601 (10)	0.0431 (8)
C9	0.1485 (8)	0.1844 (2)	0.33954 (11)	0.0571 (10)
H13	0.0117	0.1508	0.3239	0.069*
H14	0.3097	0.1452	0.3432	0.069*
C9'	1.2565 (8)	0.9325 (2)	0.40927 (9)	0.0461 (8)
H15	1.4495	0.9183	0.4152	0.055*
H16	1.2451	0.9971	0.4025	0.055*
C10	0.2340 (9)	0.2710 (2)	0.31677 (9)	0.0506 (9)
H17	0.3460	0.2543	0.2936	0.061*
H18	0.0692	0.3026	0.3072	0.061*
C10'	1.1607 (7)	0.8755 (2)	0.37343 (9)	0.0455 (8)
H19	0.9982	0.9038	0.3614	0.055*
H20	1.3072	0.8736	0.3534	0.055*
C11	−0.0325 (8)	0.3188 (3)	0.43371 (10)	0.0527 (9)
H21	0.0097	0.3756	0.4449	0.063*
C11'	0.7255 (8)	0.8244 (2)	0.47963 (9)	0.0499 (9)
H22	0.6006	0.7757	0.4791	0.060*
C12	−0.2092 (9)	0.2592 (3)	0.45375 (12)	0.0668 (11)
H23	−0.2908	0.2753	0.4781	0.080*
C12'	0.7387 (9)	0.8806 (3)	0.51317 (10)	0.0578 (10)
H24	0.6242	0.8707	0.5353	0.069*
C13	−0.2590 (9)	0.1757 (3)	0.43632 (13)	0.0660 (11)
C13'	0.9266 (9)	0.9516 (3)	0.51263 (10)	0.0581 (10)
C14	−0.1492 (8)	0.1495 (3)	0.40030 (13)	0.0615 (11)
H25	−0.1928	0.0924	0.3895	0.092*
C14'	1.0930 (8)	0.9700 (3)	0.48011 (10)	0.0551 (9)
H26	1.2141	1.0198	0.4807	0.066*
F1	−0.4347 (6)	0.11636 (19)	0.45634 (9)	0.1020 (9)
F1'	0.9452 (7)	1.00610 (18)	0.54589 (7)	0.0957 (9)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0593 (7)	0.1298 (10)	0.0587 (6)	−0.0099 (7)	−0.0044 (5)	0.0150 (6)
O1W	0.098 (3)	0.120 (3)	0.0524 (17)	0.013 (2)	−0.0059 (17)	−0.0197 (17)
O2W	0.0740 (19)	0.095 (2)	0.0626 (16)	−0.0110 (18)	0.0067 (18)	0.0175 (16)
N1	0.0506 (17)	0.0464 (15)	0.0414 (14)	−0.0137 (15)	0.0035 (14)	−0.0038 (13)
C2'	0.0459 (19)	0.0432 (19)	0.0414 (18)	−0.0070 (16)	−0.0018 (16)	−0.0028 (15)
C2	0.0390 (18)	0.0357 (17)	0.0444 (17)	−0.0061 (15)	0.0004 (15)	0.0030 (14)
C3	0.0357 (18)	0.0401 (17)	0.0411 (17)	0.0007 (16)	0.0039 (15)	−0.0046 (15)
C3'	0.0384 (18)	0.0422 (18)	0.0403 (17)	−0.0039 (16)	0.0044 (15)	0.0003 (15)
O4	0.0432 (12)	0.0465 (13)	0.0450 (12)	0.0013 (13)	−0.0060 (12)	−0.0019 (10)
O4'	0.0512 (14)	0.0442 (12)	0.0569 (13)	−0.0016 (12)	0.0125 (13)	−0.0022 (11)
C5	0.0404 (18)	0.0349 (17)	0.0456 (18)	0.0003 (15)	0.0008 (17)	−0.0006 (15)
C5'	0.0348 (17)	0.0430 (19)	0.0393 (17)	−0.0010 (15)	−0.0008 (15)	0.0007 (15)
O6	0.0562 (14)	0.0394 (12)	0.0410 (11)	−0.0112 (12)	0.0060 (12)	−0.0027 (10)
O6'	0.0437 (13)	0.0532 (14)	0.0449 (12)	−0.0116 (11)	0.0076 (11)	−0.0069 (11)
C7	0.0403 (18)	0.044 (2)	0.0424 (19)	−0.0079 (17)	−0.0072 (16)	0.0112 (16)
C7'	0.0400 (19)	0.0469 (19)	0.0365 (17)	0.0051 (17)	−0.0033 (16)	−0.0046 (15)
C8	0.0412 (19)	0.0370 (18)	0.059 (2)	−0.0038 (17)	−0.0063 (17)	0.0082 (17)
C8'	0.0386 (19)	0.0441 (19)	0.0467 (19)	0.0081 (17)	−0.0071 (16)	−0.0029 (16)
C9	0.060 (3)	0.0351 (18)	0.076 (3)	−0.0089 (18)	0.005 (2)	−0.0075 (18)
C9'	0.0445 (19)	0.0416 (18)	0.0522 (19)	−0.0056 (18)	−0.0005 (18)	0.0015 (16)
C10	0.056 (2)	0.046 (2)	0.0500 (19)	−0.008 (2)	0.003 (2)	−0.0102 (16)
C10'	0.049 (2)	0.0463 (19)	0.0408 (18)	−0.0076 (16)	−0.0002 (16)	0.0044 (15)
C11	0.058 (2)	0.055 (2)	0.045 (2)	−0.012 (2)	0.0019 (19)	0.0034 (18)
C11'	0.051 (2)	0.055 (2)	0.0446 (19)	0.0013 (19)	0.0068 (18)	0.0017 (16)
C12	0.060 (3)	0.078 (3)	0.062 (2)	−0.011 (2)	0.007 (2)	0.016 (2)
C12'	0.058 (2)	0.072 (2)	0.0435 (19)	0.016 (2)	0.0081 (19)	0.0023 (19)
C13	0.055 (2)	0.060 (2)	0.084 (3)	−0.020 (2)	0.001 (2)	0.027 (2)
C13'	0.068 (3)	0.065 (3)	0.041 (2)	0.008 (2)	−0.001 (2)	−0.0143 (19)
C14	0.054 (2)	0.048 (2)	0.082 (3)	−0.0118 (19)	−0.008 (2)	0.009 (2)
C14'	0.059 (2)	0.051 (2)	0.056 (2)	−0.002 (2)	−0.007 (2)	−0.0113 (18)
F1	0.090 (2)	0.0920 (18)	0.124 (2)	−0.0404 (17)	0.0217 (17)	0.0312 (17)
F1'	0.124 (2)	0.1009 (19)	0.0617 (14)	−0.0078 (18)	0.0089 (15)	−0.0367 (14)

Geometric parameters (Å, º) top

O1W—H1B	0.89 (4)	C7—C8	1.402 (5)
O1W—H2B	0.88 (3)	C7'—C11'	1.378 (5)
O2W—H1A	0.89 (4)	C7'—C8'	1.388 (5)
O2W—H2A	0.92 (5)	C8—C14	1.391 (5)
N1—C2'	1.479 (4)	C8—C9	1.496 (5)
N1—C2	1.493 (4)	C8'—C14'	1.400 (5)
N1—H1	0.9000	C8'—C9'	1.511 (5)
N1—H2	0.9000	C9—C10	1.528 (5)
C2'—C3'	1.512 (4)	C9—H13	0.9700
C2'—H3	0.9700	C9—H14	0.9700
C2'—H4	0.9700	C9'—C10'	1.525 (4)
C2—C3	1.512 (4)	C9'—H15	0.9700
C2—H5	0.9700	C9'—H16	0.9700
C2—H6	0.9700	C10—H17	0.9700
C3—O4	1.424 (4)	C10—H18	0.9700
C3—C5	1.524 (4)	C10'—H19	0.9700
C3—H7	0.9800	C10'—H20	0.9700
C3'—O4'	1.422 (4)	C11—C12	1.385 (5)
C3'—C5'	1.528 (4)	C11—H21	0.9300
C3'—H8	0.9800	C11'—C12'	1.386 (5)
O4—H9	0.8200	C11'—H22	0.9300
O4'—H10	0.8200	C12—C13	1.370 (6)
C5—O6	1.442 (4)	C12—H23	0.9300
C5—C10	1.506 (5)	C12'—C13'	1.372 (5)
C5—H11	0.9800	C12'—H24	0.9300
C5'—O6'	1.434 (4)	C13—C14	1.363 (6)
C5'—C10'	1.505 (4)	C13—F1	1.379 (4)
C5'—H12	0.9800	C13'—C14'	1.371 (5)
O6—C7	1.373 (4)	C13'—F1'	1.365 (4)
O6'—C7'	1.386 (4)	C14—H25	0.9300
C7—C11	1.377 (5)	C14'—H26	0.9300

H1B—O1W—H2B	102 (4)	C14—C8—C7	117.1 (3)
H1A—O2W—H2A	101 (4)	C14—C8—C9	122.1 (3)
C2'—N1—C2	111.6 (2)	C7—C8—C9	120.7 (3)
C2'—N1—H1	109.3	C7'—C8'—C14'	117.2 (3)
C2—N1—H1	109.3	C7'—C8'—C9'	121.1 (3)
C2'—N1—H2	109.3	C14'—C8'—C9'	121.7 (3)
C2—N1—H2	109.3	C8—C9—C10	110.6 (3)
H1—N1—H2	108.0	C8—C9—H13	109.5
N1—C2'—C3'	113.5 (3)	C10—C9—H13	109.5
N1—C2'—H3	108.9	C8—C9—H14	109.5
C3'—C2'—H3	108.9	C10—C9—H14	109.5
N1—C2'—H4	108.9	H13—C9—H14	108.1
C3'—C2'—H4	108.9	C8'—C9'—C10'	111.4 (3)
H3—C2'—H4	107.7	C8'—C9'—H15	109.3
N1—C2—C3	112.8 (2)	C10'—C9'—H15	109.3
N1—C2—H5	109.0	C8'—C9'—H16	109.3
C3—C2—H5	109.0	C10'—C9'—H16	109.3
N1—C2—H6	109.0	H15—C9'—H16	108.0
C3—C2—H6	109.0	C5—C10—C9	110.3 (3)
H5—C2—H6	107.8	C5—C10—H17	109.6
O4—C3—C2	108.0 (2)	C9—C10—H17	109.6
O4—C3—C5	111.9 (3)	C5—C10—H18	109.6
C2—C3—C5	109.3 (2)	C9—C10—H18	109.6
O4—C3—H7	109.2	H17—C10—H18	108.1
C2—C3—H7	109.2	C5'—C10'—C9'	110.5 (3)
C5—C3—H7	109.2	C5'—C10'—H19	109.5
O4'—C3'—C2'	107.7 (3)	C9'—C10'—H19	109.5
O4'—C3'—C5'	110.4 (3)	C5'—C10'—H20	109.5
C2'—C3'—C5'	111.1 (2)	C9'—C10'—H20	109.5
O4'—C3'—H8	109.2	H19—C10'—H20	108.1
C2'—C3'—H8	109.2	C7—C11—C12	120.2 (3)
C5'—C3'—H8	109.2	C7—C11—H21	119.9
C3—O4—H9	109.5	C12—C11—H21	119.9
C3'—O4'—H10	109.5	C7'—C11'—C12'	120.3 (4)
O6—C5—C10	111.3 (3)	C7'—C11'—H22	119.9
O6—C5—C3	105.6 (2)	C12'—C11'—H22	119.9
C10—C5—C3	114.5 (3)	C13—C12—C11	117.5 (4)
O6—C5—H11	108.4	C13—C12—H23	121.3
C10—C5—H11	108.4	C11—C12—H23	121.3
C3—C5—H11	108.4	C13'—C12'—C11'	117.7 (4)
O6'—C5'—C10'	110.5 (3)	C13'—C12'—H24	121.1
O6'—C5'—C3'	105.8 (2)	C11'—C12'—H24	121.1
C10'—C5'—C3'	114.4 (3)	C14—C13—C12	123.5 (4)
O6'—C5'—H12	108.7	C14—C13—F1	119.1 (4)
C10'—C5'—H12	108.7	C12—C13—F1	117.4 (4)
C3'—C5'—H12	108.7	C14'—C13'—F1'	119.1 (4)
C7—O6—C5	117.8 (2)	C14'—C13'—C12'	122.7 (3)
C7'—O6'—C5'	116.2 (2)	F1'—C13'—C12'	118.1 (3)
O6—C7—C11	115.7 (3)	C13—C14—C8	119.9 (4)
O6—C7—C8	122.4 (3)	C13—C14—H25	120.1
C11—C7—C8	121.8 (3)	C8—C14—H25	120.1
C11'—C7'—O6'	115.8 (3)	C13'—C14'—C8'	120.0 (4)
C11'—C7'—C8'	122.0 (3)	C13'—C14'—H26	120.0
O6'—C7'—C8'	122.1 (3)	C8'—C14'—H26	120.0

C2—N1—C2'—C3'	175.4 (3)	O6'—C7'—C8'—C9'	0.8 (5)
C2'—N1—C2—C3	179.6 (3)	C14—C8—C9—C10	157.4 (4)
N1—C2—C3—O4	−56.6 (3)	C7—C8—C9—C10	−19.6 (5)
N1—C2—C3—C5	−178.5 (3)	C7'—C8'—C9'—C10'	11.8 (4)
N1—C2'—C3'—O4'	−70.0 (4)	C14'—C8'—C9'—C10'	−167.6 (3)
N1—C2'—C3'—C5'	169.0 (3)	O6—C5—C10—C9	−59.5 (4)
O4—C3—C5—O6	−64.8 (3)	C3—C5—C10—C9	−179.1 (3)
C2—C3—C5—O6	54.8 (3)	C8—C9—C10—C5	47.3 (4)
O4—C3—C5—C10	58.0 (4)	O6'—C5'—C10'—C9'	61.2 (4)
C2—C3—C5—C10	177.5 (3)	C3'—C5'—C10'—C9'	−179.6 (3)
O4'—C3'—C5'—O6'	−167.0 (2)	C8'—C9'—C10'—C5'	−41.4 (4)
C2'—C3'—C5'—O6'	−47.6 (3)	O6—C7—C11—C12	175.8 (3)
O4'—C3'—C5'—C10'	71.1 (4)	C8—C7—C11—C12	−1.5 (5)
C2'—C3'—C5'—C10'	−169.5 (3)	O6'—C7'—C11'—C12'	179.9 (3)
C10—C5—O6—C7	41.9 (4)	C8'—C7'—C11'—C12'	−2.0 (5)
C3—C5—O6—C7	166.7 (3)	C7—C11—C12—C13	1.5 (6)
C10'—C5'—O6'—C7'	−49.5 (4)	C7'—C11'—C12'—C13'	−0.1 (5)
C3'—C5'—O6'—C7'	−173.9 (2)	C11—C12—C13—C14	−1.4 (7)
C5—O6—C7—C11	170.0 (3)	C11—C12—C13—F1	179.9 (3)
C5—O6—C7—C8	−12.7 (4)	C11'—C12'—C13'—C14'	1.9 (6)
C5'—O6'—C7'—C11'	−163.3 (3)	C11'—C12'—C13'—F1'	−178.6 (3)
C5'—O6'—C7'—C8'	18.7 (4)	C12—C13—C14—C8	1.3 (7)
O6—C7—C8—C14	−175.8 (3)	F1—C13—C14—C8	180.0 (3)
C11—C7—C8—C14	1.3 (5)	C7—C8—C14—C13	−1.2 (5)
O6—C7—C8—C9	1.4 (5)	C9—C8—C14—C13	−178.3 (4)
C11—C7—C8—C9	178.5 (3)	F1'—C13'—C14'—C8'	178.8 (3)
C11'—C7'—C8'—C14'	2.2 (5)	C12'—C13'—C14'—C8'	−1.7 (6)
O6'—C7'—C8'—C14'	−179.8 (3)	C7'—C8'—C14'—C13'	−0.4 (5)
C11'—C7'—C8'—C9'	−177.2 (3)	C9'—C8'—C14'—C13'	179.0 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1Wⁱ	0.90	2.12	2.794 (3)	131
N1—H1···O4ⁱⁱ	0.90	2.37	3.056 (4)	133
N1—H2···O4′ⁱⁱⁱ	0.90	2.19	3.061 (4)	162
O4—H9···Cl1ⁱ	0.82	2.67	3.142 (2)	118
O4′—H10···O2Wⁱⁱ	0.82	2.04	2.701 (4)	137
O1W—H1B···Cl1	0.89 (4)	2.47 (4)	3.242 (2)	146 (4)
O1W—H2B···N1^iv	0.88 (3)	2.47 (4)	2.794 (3)	102 (3)
O2W—H1A···Cl1	0.89 (4)	2.29 (4)	3.175 (3)	175 (3)
O2W—H2A···Cl1ⁱⁱⁱ	0.88 (4)	2.37 (4)	3.242 (3)	171 (3)
C2′—H4···O6′	0.97	2.26	2.708 (4)	107
C2—H5···O6	0.97	2.35	2.738 (4)	103
C2—H6···O6ⁱⁱ	0.97	2.49	3.457 (4)	172
C14′—H26···F1^v	0.93	2.34	3.213 (5)	156

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

Experimental details

Crystal data
Chemical formula	C₂₂H₂₆F₂NO₄⁺·Cl⁻·2H₂O
M_r	477.92
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	291
a, b, c (Å)	4.8026 (4), 14.5781 (12), 33.261 (3)
V (Å³)	2328.7 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.22
Crystal size (mm)	0.60 × 0.12 × 0.09

Data collection
Diffractometer	APEX CCD area-detector
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.865, 0.981
No. of measured, independent and observed [I > 2σ(I)] reflections	26222, 3401, 2857
R_int	0.054
(sin θ/λ)_max (Å⁻¹)	0.626

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.041, 0.113, 1.05
No. of reflections	3401
No. of parameters	301
No. of restraints	6
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.33, −0.24
Absolute structure	Flack (1983), xx Friedel pairs
Absolute structure parameter	−0.04 (12)

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEPIII (Burnett & Johnson, 1996), SHELXTL (Bruker, 2001).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1Wⁱ	0.90	2.12	2.794 (3)	131
N1—H1···O4ⁱⁱ	0.90	2.37	3.056 (4)	133
N1—H2···O4'ⁱⁱⁱ	0.90	2.19	3.061 (4)	162
O4—H9···Cl1ⁱ	0.82	2.67	3.142 (2)	118
O4'—H10···O2Wⁱⁱ	0.82	2.04	2.701 (4)	137
O1W—H1B···Cl1	0.89 (4)	2.47 (4)	3.242 (2)	146 (4)
O1W—H2B···N1^iv	0.88 (3)	2.47 (4)	2.794 (3)	102 (3)
O2W—H1A···Cl1	0.89 (4)	2.29 (4)	3.175 (3)	175 (3)
O2W—H2A···Cl1ⁱⁱⁱ	0.88 (4)	2.37 (4)	3.242 (3)	171 (3)
C2'—H4···O6'	0.97	2.26	2.708 (4)	107
C2—H5···O6	0.97	2.35	2.738 (4)	103
C2—H6···O6ⁱⁱ	0.97	2.49	3.457 (4)	172
C14'—H26···F1^v	0.93	2.34	3.213 (5)	156

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

References

Bruker (2001). SMART, SAINT, SADABS and SHELXTL. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA. Google Scholar
Cini, M., Crotti, P. & Macchia, F. (1990). Tetrahedron Lett. 31, 4661–4664. Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Lommen, G. R. E. van, de Bruyn, M. F. L. & Schroven, M. F. J. (1990). J. Pharm. Belg. 45, 355–360. PubMed Google Scholar
Peeters, O. M., Blaton, N. M. & De Ranter, C. J. (1993). Acta Cryst. C49, 2154–2157. CSD CrossRef CAS Web of Science IUCr Journals Google Scholar
Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany. Google Scholar
Tuchalski, G., Emmerling, F., Groger, K., Hansicke, A., Nagel, T. & Reck, G. (2006). J. Mol. Struct. 800, 28–44. Web of Science CSD CrossRef CAS Google Scholar

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