Duloxetine hydro-chloride.

THE TITLE COMPOUND [SYSTEMATIC NAME: N-methyl-3-(1-naphth-yloxy)-3-(2-thien-yl)propan-1-aminium chloride], C(18)H(20)NOS(+)·Cl(-), was crystallized from 1,4-dioxane. Twofold rotational disorder exhibited by the thio-phene ring in a 0.580 (5):0.420 (5) ratio represents two different conformations of the mol-ecule that exist in the same crystal form. The crystal structure contains strong N-H⋯Cl hydrogen bonds.

Related literature

For therapeutic properties of duloxetine hydro­chloride, see Waitekus & Kirkpatrick (2004 ▶). For related structures, see: Brenna et al. (2007 ▶); Tao et al. (2008 ▶). The title compound is reported to have different polymorphs on the basis of X-ray powder diffraction data, see: Ini et al. (2006 ▶).

Experimental

Crystal data

C18H20NOS+·Cl−

M = 333.86

Monoclinic,

a = 9.7453 (10) Å

b = 6.9227 (7) Å

c = 13.4247 (16) Å

β = 109.432 (4)°

V = 854.09 (16) Å3

Z = 2

Mo Kα radiation

μ = 0.35 mm−1

T = 150 K

0.38 × 0.08 × 0.03 mm

Data collection

Bruker Kappa APEXII CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 2003 ▶) T min = 0.879, T max = 0.990

6386 measured reflections

2947 independent reflections

2255 reflections with I > 2σ(I)

R int = 0.058

Refinement

R[F 2 > 2σ(F 2)] = 0.044

wR(F 2) = 0.131

S = 0.79

2947 reflections

237 parameters

110 restraints

H-atom parameters constrained

Δρmax = 0.17 e Å−3

Δρmin = −0.21 e Å−3

Absolute structure: Flack (1983 ▶), 1309 Friedel pairs

Flack parameter: −0.05 (10)

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL-Plus (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809033996/bg2289sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809033996/bg2289Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C18H20NOS+·Cl−	F(000) = 352
Mr = 333.86	Dx = 1.298 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 1635 reflections
a = 9.7453 (10) Å	θ = 2.3–22.1°
b = 6.9227 (7) Å	µ = 0.35 mm−1
c = 13.4247 (16) Å	T = 150 K
β = 109.432 (4)°	Thin Plates, colourless
V = 854.09 (16) Å3	0.38 × 0.08 × 0.03 mm
Z = 2

Bruker Kappa APEXII CCD area-detector diffractometer	2947 independent reflections
Radiation source: fine-focus sealed tube	2255 reflections with I > 2σ(I)
graphite	Rint = 0.058
φ scans, and ω scans with κ offsets	θmax = 25.0°, θmin = 1.6°
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	h = −10→11
Tmin = 0.879, Tmax = 0.990	k = −8→8
6386 measured reflections	l = −15→15

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) = 0.131	w = 1/[σ2(Fo2) + (0.1P)2 + 0.0292P] where P = (Fo2 + 2Fc2)/3
S = 0.79	(Δ/σ)max = 0.005
2947 reflections	Δρmax = 0.17 e Å−3
237 parameters	Δρmin = −0.21 e Å−3
110 restraints	Absolute structure: Flack (1983), 1309 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: −0.05 (10)

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.

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.7076 (5)	1.0388 (6)	0.3732 (3)	0.0414 (10)
H1	0.6473	1.0546	0.3018	0.050*
C2	0.8113 (5)	1.1721 (7)	0.4181 (3)	0.0559 (13)
H2	0.8222	1.2804	0.3779	0.067*
C3	0.9031 (5)	1.1525 (7)	0.5234 (3)	0.0498 (12)
H3	0.9769	1.2456	0.5538	0.060*
C4	0.8856 (4)	0.9990 (6)	0.5818 (3)	0.0404 (10)
H4	0.9465	0.9877	0.6534	0.048*
C5	0.7784 (4)	0.8557 (6)	0.5376 (2)	0.0333 (8)
C6	0.7619 (5)	0.6944 (7)	0.5957 (3)	0.0488 (12)
H6	0.8217	0.6804	0.6674	0.059*
C7	0.6613 (5)	0.5596 (7)	0.5500 (3)	0.0594 (14)
H7	0.6518	0.4508	0.5904	0.071*
C8	0.5696 (5)	0.5748 (7)	0.4444 (3)	0.0453 (11)
H8	0.5007	0.4764	0.4134	0.054*
C9	0.5811 (4)	0.7331 (5)	0.3870 (3)	0.0302 (9)
C10	0.6874 (4)	0.8761 (5)	0.4309 (3)	0.0285 (8)
C11	0.3962 (4)	0.6244 (5)	0.2248 (3)	0.0287 (8)
H11	0.3506	0.5543	0.2709	0.034*
C16	0.2800 (4)	0.7340 (5)	0.1395 (3)	0.0334 (9)
H16A	0.2233	0.6416	0.0851	0.040*
H16B	0.3277	0.8263	0.1051	0.040*
C17	0.1769 (4)	0.8439 (7)	0.1826 (3)	0.0395 (9)
H17A	0.1988	0.8111	0.2581	0.047*
H17B	0.1925	0.9844	0.1776	0.047*
C18	−0.0810 (4)	0.8802 (6)	0.1698 (3)	0.0449 (10)
H18A	−0.0634	0.8265	0.2405	0.067*
H18B	−0.1802	0.8483	0.1246	0.067*
H18C	−0.0694	1.0209	0.1746	0.067*
Cl1	0.02776 (10)	0.35210 (15)	0.11567 (7)	0.0385 (3)
N1	0.0237 (3)	0.7976 (4)	0.1242 (2)	0.0334 (7)
H1A	0.0015	0.8416	0.0560	0.040*
H1B	0.0131	0.6655	0.1214	0.040*
O1	0.4920 (3)	0.7711 (3)	0.28494 (18)	0.0335 (6)
C12	0.4783 (4)	0.4840 (6)	0.1806 (3)	0.0304 (9)
S1A	0.4000 (4)	0.2836 (6)	0.1112 (4)	0.0390 (8)	0.580 (5)
C13A	0.5587 (15)	0.220 (3)	0.088 (2)	0.043 (2)	0.580 (5)
H13A	0.5703	0.1075	0.0508	0.051*	0.58
C14A	0.6634 (16)	0.353 (2)	0.1292 (18)	0.045 (2)	0.580 (5)
H14A	0.7575	0.3491	0.1227	0.054*	0.58
C15A	0.6158 (17)	0.500 (3)	0.184 (2)	0.042 (4)	0.580 (5)
H15A	0.6774	0.6027	0.2199	0.051*	0.58
S1B	0.6515 (6)	0.5208 (10)	0.1826 (7)	0.0410 (14)	0.420 (5)
C13B	0.656 (2)	0.310 (3)	0.119 (2)	0.042 (3)	0.420 (5)
H13B	0.7390	0.2624	0.1043	0.051*	0.42
C14B	0.526 (2)	0.221 (4)	0.091 (3)	0.045 (3)	0.420 (5)
H14B	0.5030	0.1062	0.0498	0.054*	0.42
C15B	0.427 (2)	0.318 (3)	0.131 (2)	0.053 (5)	0.420 (5)
H15B	0.3325	0.2691	0.1237	0.063*	0.42

	U11	U22	U33	U12	U13	U23
C12	0.030 (2)	0.034 (2)	0.0272 (18)	−0.0013 (18)	0.0086 (16)	0.0036 (16)
S1A	0.0360 (14)	0.0354 (13)	0.0453 (18)	0.0021 (11)	0.0130 (14)	−0.0108 (10)
C13A	0.046 (6)	0.048 (5)	0.038 (5)	0.018 (5)	0.019 (6)	−0.002 (4)
C14A	0.039 (4)	0.060 (7)	0.042 (5)	0.009 (4)	0.021 (4)	−0.001 (5)
C15A	0.044 (9)	0.049 (6)	0.042 (5)	−0.005 (6)	0.025 (6)	−0.001 (4)
S1B	0.024 (2)	0.056 (2)	0.042 (2)	−0.0013 (18)	0.0099 (19)	0.0093 (17)
C13B	0.042 (5)	0.051 (6)	0.037 (7)	0.009 (5)	0.017 (5)	0.015 (5)
C14B	0.045 (7)	0.050 (6)	0.036 (6)	0.005 (6)	0.010 (6)	0.003 (5)
C15B	0.043 (7)	0.062 (12)	0.055 (11)	0.005 (7)	0.018 (8)	0.003 (8)
C1	0.047 (2)	0.038 (2)	0.0303 (19)	−0.007 (2)	0.0003 (18)	0.0082 (18)
C2	0.062 (3)	0.048 (3)	0.043 (2)	−0.020 (3)	−0.002 (2)	0.010 (2)
C3	0.051 (3)	0.045 (3)	0.043 (2)	−0.017 (2)	0.002 (2)	−0.003 (2)
C4	0.040 (2)	0.046 (2)	0.0269 (19)	−0.002 (2)	−0.0007 (17)	−0.0027 (19)
C5	0.034 (2)	0.0372 (19)	0.0269 (17)	−0.003 (2)	0.0081 (15)	−0.001 (2)
C6	0.046 (3)	0.058 (3)	0.032 (2)	−0.010 (2)	−0.0012 (19)	0.019 (2)
C7	0.060 (3)	0.061 (3)	0.042 (2)	−0.020 (3)	−0.004 (2)	0.028 (2)
C8	0.044 (2)	0.043 (2)	0.040 (2)	−0.014 (2)	0.0024 (19)	0.010 (2)
C9	0.032 (2)	0.032 (2)	0.0261 (18)	0.0051 (17)	0.0090 (15)	0.0010 (15)
C10	0.0295 (19)	0.031 (2)	0.0250 (16)	0.0001 (17)	0.0092 (14)	−0.0023 (16)
C11	0.026 (2)	0.031 (2)	0.0268 (18)	−0.0037 (15)	0.0066 (16)	0.0011 (14)
C16	0.029 (2)	0.035 (2)	0.0308 (19)	0.0003 (18)	0.0029 (16)	−0.0060 (16)
C17	0.033 (2)	0.040 (2)	0.0382 (19)	0.002 (2)	0.0021 (16)	−0.015 (2)
C18	0.039 (2)	0.040 (2)	0.060 (2)	0.003 (2)	0.023 (2)	0.000 (2)
Cl1	0.0438 (6)	0.0345 (5)	0.0345 (5)	−0.0070 (5)	0.0095 (4)	0.0009 (4)
N1	0.0348 (17)	0.0295 (17)	0.0335 (16)	−0.0006 (14)	0.0080 (14)	0.0003 (13)
O1	0.0365 (14)	0.0308 (13)	0.0254 (12)	−0.0054 (12)	−0.0003 (11)	−0.0003 (10)

C1—C2	1.353 (6)	C17—H17A	0.9900
C1—C10	1.418 (5)	C17—H17B	0.9900
C1—H1	0.9500	C18—N1	1.469 (5)
C2—C3	1.406 (5)	C18—H18A	0.9800
C2—H2	0.9500	C18—H18B	0.9800
C3—C4	1.364 (6)	C18—H18C	0.9800
C3—H3	0.9500	N1—H1A	0.9200
C4—C5	1.420 (6)	N1—H1B	0.9200
C4—H4	0.9500	C12—C15A	1.332 (14)
C5—C6	1.402 (6)	C12—C15B	1.341 (16)
C5—C10	1.418 (4)	C12—C11	1.501 (5)
C6—C7	1.344 (6)	C12—S1B	1.699 (7)
C6—H6	0.9500	C12—S1A	1.703 (5)
C7—C8	1.406 (5)	S1A—C13A	1.734 (10)
C7—H7	0.9500	C13A—C14A	1.351 (10)
C8—C9	1.365 (5)	C13A—H13A	0.9500
C8—H8	0.9500	C14A—C15A	1.420 (14)
C9—O1	1.381 (4)	C14A—H14A	0.9500
C9—C10	1.413 (5)	C15A—H15A	0.9500
C11—O1	1.433 (4)	S1B—C13B	1.699 (14)
C11—C16	1.519 (5)	C13B—C14B	1.351 (11)
C11—H11	1.0000	C13B—H13B	0.9500
C16—C17	1.520 (5)	C14B—C15B	1.421 (15)
C16—H16A	0.9900	C14B—H14B	0.9500
C16—H16B	0.9900	C15B—H15B	0.9500
C17—N1	1.472 (4)
C2—C1—C10	121.2 (3)	N1—C17—H17B	109.3
C2—C1—H1	119.4	C16—C17—H17B	109.3
C10—C1—H1	119.4	H17A—C17—H17B	107.9
C1—C2—C3	120.9 (4)	N1—C18—H18A	109.5
C1—C2—H2	119.5	N1—C18—H18B	109.5
C3—C2—H2	119.5	H18A—C18—H18B	109.5
C4—C3—C2	119.5 (4)	N1—C18—H18C	109.5
C4—C3—H3	120.2	H18A—C18—H18C	109.5
C2—C3—H3	120.2	H18B—C18—H18C	109.5
C3—C4—C5	121.3 (3)	C18—N1—C17	114.6 (3)
C3—C4—H4	119.3	C18—N1—H1A	108.6
C5—C4—H4	119.3	C17—N1—H1A	108.6
C6—C5—C10	119.5 (4)	C18—N1—H1B	108.6
C6—C5—C4	121.9 (3)	C17—N1—H1B	108.6
C10—C5—C4	118.6 (3)	H1A—N1—H1B	107.6
C7—C6—C5	120.0 (4)	C9—O1—C11	120.0 (3)
C7—C6—H6	120.0	C15A—C12—C15B	107.3 (10)
C5—C6—H6	120.0	C15A—C12—C11	126.5 (7)
C6—C7—C8	122.0 (4)	C15B—C12—C11	126.2 (8)
C6—C7—H7	119.0	C15B—C12—S1B	110.1 (8)
C8—C7—H7	119.0	C11—C12—S1B	123.7 (3)
C9—C8—C7	119.0 (4)	C15A—C12—S1A	110.5 (7)
C9—C8—H8	120.5	C11—C12—S1A	122.9 (3)
C7—C8—H8	120.5	S1B—C12—S1A	113.1 (3)
C8—C9—O1	124.8 (3)	C12—S1A—C13A	92.4 (4)
C8—C9—C10	120.9 (3)	C14A—C13A—S1A	110.4 (8)
O1—C9—C10	114.4 (3)	C14A—C13A—H13A	124.8
C9—C10—C1	123.0 (3)	S1A—C13A—H13A	124.8
C9—C10—C5	118.5 (3)	C13A—C14A—C15A	111.8 (10)
C1—C10—C5	118.5 (3)	C13A—C14A—H14A	124.1
O1—C11—C12	110.4 (3)	C15A—C14A—H14A	124.1
O1—C11—C16	104.7 (3)	C12—C15A—C14A	114.8 (11)
C12—C11—C16	112.8 (3)	C12—C15A—H15A	122.6
O1—C11—H11	109.6	C14A—C15A—H15A	122.6
C12—C11—H11	109.6	C13B—S1B—C12	93.3 (7)
C16—C11—H11	109.6	C14B—C13B—S1B	110.6 (11)
C11—C16—C17	112.6 (3)	C14B—C13B—H13B	124.7
C11—C16—H16A	109.1	S1B—C13B—H13B	124.7
C17—C16—H16A	109.1	C13B—C14B—C15B	112.1 (12)
C11—C16—H16B	109.1	C13B—C14B—H14B	124.0
C17—C16—H16B	109.1	C15B—C14B—H14B	124.0
H16A—C16—H16B	107.8	C12—C15B—C14B	113.7 (12)
N1—C17—C16	111.7 (3)	C12—C15B—H15B	123.2
N1—C17—H17A	109.3	C14B—C15B—H15B	123.2
C16—C17—H17A	109.3

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···Cl1i	0.92	2.23	3.113 (3)	161
N1—H1B···Cl1	0.92	2.18	3.087 (3)	170

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯Cl1i	0.92	2.23	3.113 (3)	161
N1—H1B⋯Cl1	0.92	2.18	3.087 (3)	170

Symmetry code: (i) .