Clostebol acetate

Maccaroni, E.; Mele, A.; Del Rosso, R.; Malpezzi, L.

doi:10.1107/S1600536811026560

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 67| Part 8| August 2011| Pages o1952-o1953

doi:10.1107/S1600536811026560

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Clostebol acetate

Elisabetta Maccaroni,^a Andrea Mele,^a Renato Del Rosso ^a and Luciana Malpezzi ^a ^*

^aDepartment of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico di Milano, Via Mancinelli 7, I-20131 Milano, Italy
^*Correspondence e-mail: luciana.malpezzi@polimi.it

(Received 13 June 2011; accepted 4 July 2011; online 9 July 2011)

The title compound, C₂₁H₂₉ClO₃ [systematic name (8R,9S,10R,13S,14S,17S)-4-chloro-3-oxoandrost-4-en-17β-yl acetate], is a 4-chloro derivative of testosterone, used as an anabolic androgenic agent or applied topically in ophthalmological and dermatological treatments. The absolute configurations at positions 8, 9, 10, 13, 14 and 17 were established by refinement of the Flack parameter as R, S, R, S, S, and S, respectively. Rings B and C of the steroid ring system adopt chair conformations, ring A has a half-chair conformation, while ring D is in a C₁₃ envelope conformation. Ring B and C, and C and D are trans fused. In the crystal, molecules are linked by a weak C—H⋯O interaction.

Related literature

For the characterization of related structures, see Duax et al. (1971 ); Böcskei et al. (1996 ); Verma et al. (2006 ). For the synthesis by direct (or via epoxide) chlorination of the 4 carbon atom of the testosterone molecule, see: Camerino et al. (1956 ); Julian Laboratories Inc. Illinois (1960 ); Società Farmaceutici Italia (1960 ). For physiological properties when used topically in dermatological and ophthalmological treatments and by application of an anabolic drug, see: Sweetman (2009 ). For standard bond lengths, see: Allen et al. (1987 ) and for ring puckering parameters, see: Cremer & Pople (1975 ).

Experimental

Crystal data

C₂₁H₂₉ClO₃
M_r = 364.89
Orthorhombic, P 2₁ 2₁ 2₁
a = 7.740 (1) Å
b = 12.631 (2) Å
c = 19.275 (2) Å
V = 1884.4 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 295 K
0.26 × 0.11 × 0.10 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ) T_min = 0.945, T_max = 0.978
8471 measured reflections
3325 independent reflections
2586 reflections with I > 2σ(I)
R_int = 0.032

Refinement

R[F² > 2σ(F²)] = 0.038
wR(F²) = 0.079
S = 0.97
3325 reflections
242 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.15 e Å⁻³
Absolute structure: Flack (1983 ), 1392 Friedel pairs
Flack parameter: −0.02 (6)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C6—H6B⋯O1ⁱ	0.97	2.62	3.565 (3)	166
Symmetry code: (i) $[-x, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Data collection: SMART (Bruker, 2003 ); cell refinement: SAINT (Bruker, 2003); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: SHELXTL/NT (Sheldrick, 2008); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811026560/zl2382sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811026560/zl2382Isup2.hkl

checkCIF report

Comment top

Clostebol acetate (Fig. 1), systematic name: (8R,9S,10R,13S,14S,17S)-4-chloro-3-oxoandrost-4-en-17β-yl acetate, is a 4-chloro derivative of testosterone, used as an anabolic androgenic agent or applied topically in ophthalmological and dermatological treatments (Sweetman, 2009). The dermal preparations of this steroid are usually used in the treatment of wounds and ulcers. The absolute configuration has been determined by refinement of the Flack parameter (Flack, 1983) which converged to -0.02 (6). Ring B and C, and C and D are trans fused. Ring A (C1—C5, C10) of the steroid ring system adopts a half chair conformation with puckering parameters (Cremer and Pople, 1975) of Q (total puckering amplitude) = 0.466 (3) Å, θ (azimuthal angle) = 56.4 (4)°, ϕ (phase angle) = 20.0 (4)°. Ring B (C5—C10) and C (C8, C9, C11—C14) are in chair conformations [ring B: Q = 0.543 (2) Å, θ = 2.0 (2)°, ϕ = 150 (6)°; ring C: Q = 0.575 (2) Å, θ = 3.4 (2)°, ϕ = 295 (3)°]. The five-membered ring D (C13—C17) is in a C₁₃ envelope conformation with puckering amplitude q₂ =0.455 (2)Å and phase angle ϕ₂ = 189.0 (3)°. Bond lengths and valency angles are within the range of expected values for these types of compounds (Allen et al., 1987, Böcskei et al., 1996, Duax et al., 1971, Verma et al., 2006). The acetate group is equatorially attached to the D ring and its orientation may be described by the torsion angle C17—O2—C20—O3 (0.1 (3)°).

In the crystal the molecules are linked by C—H···O weak interactions [C6—H6B···O1 = 166°; C6···O1 = 3.565 (3) Å; H6B···O1= 2.62 Å] to form chains in a herringbone arrangement running parallel to the b axis (Fig. 2).

Related literature top

For the characterization of related structures, see Duax et al. (1971); Böcskei et al. (1996); Verma et al. (2006). For the synthesis by direct (or via epoxide) chlorination of the 4 carbon atom of the testosterone molecule, see: Camerino et al. (1956); Julian Laboratories Inc. Illinois (1960); Società Farmaceutici Italia (1960). For physiological properties when used topically in dermatological and ophthalmological treatments and by application of an anabolic drug, see: Sweetman (2009). For standard bond lengths, see: Allen et al. (1987) and for ring puckering parameters, see: Cremer & Pople (1975).

Experimental top

The title compound was obtained by direct or via epoxide chlorination on the carbon atom in the 4 position of the testosterone acetate (Camerino et al., 1956, Julian Laboratories, 1960, Società Farmaceutici Italia, 1960). The purification of the crude product was carried out by selective crystallization. Single crystals were obtained from a methanol supersaturated solution at ambient temperature.

Computing details top

Data collection: SMART (Bruker, 2003); cell refinement: SAINT (Bruker, 2003); data reduction: SAINT (Bruker, 2003); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL/NT (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

	Fig. 1. Molecular structure of clostebol acetate with the atomic numbering. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. Crystal packing of clostebol acetate viewed along the a axis. Intermolecular C—H···O weak interactions are shown by dashed lines.
	Fig. 3. Crystal packing of clostebol acetate viewed along the b axis.

(8R,9S,10R,13S,14S,17S)-4-chloro- 3-oxoandrost-4-en-17β-yl acetate top

Crystal data top

C₂₁H₂₉ClO₃	D_x = 1.286 Mg m⁻³
M_r = 364.89	Mo Kα radiation, λ = 0.71069 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 3284 reflections
a = 7.740 (1) Å	θ = 2.7–24°
b = 12.631 (2) Å	µ = 0.22 mm⁻¹
c = 19.275 (2) Å	T = 295 K
V = 1884.4 (4) Å³	Prism, colourless
Z = 4	0.26 × 0.11 × 0.10 mm
F(000) = 784

Data collection top

Bruker SMART APEX CCD area-detector diffractometer	3325 independent reflections
Radiation source: fine-focus sealed tube	2586 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.032
ϕ and ω scans	θ_max = 25.1°, θ_min = 1.9°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −7→9
T_min = 0.945, T_max = 0.978	k = −13→14
8471 measured reflections	l = −23→17

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.038	w = 1/[σ²(F_o²) + (0.0396P)²] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.079	(Δ/σ)_max = 0.035
S = 0.97	Δρ_max = 0.17 e Å⁻³
3325 reflections	Δρ_min = −0.15 e Å⁻³
242 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0024 (7)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 1392 Friedel pairs
Secondary atom site location: difference Fourier map	Absolute structure parameter: −0.02 (6)

Crystal data top

C₂₁H₂₉ClO₃	V = 1884.4 (4) Å³
M_r = 364.89	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 7.740 (1) Å	µ = 0.22 mm⁻¹
b = 12.631 (2) Å	T = 295 K
c = 19.275 (2) Å	0.26 × 0.11 × 0.10 mm

Data collection top

Bruker SMART APEX CCD area-detector diffractometer	3325 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	2586 reflections with I > 2σ(I)
T_min = 0.945, T_max = 0.978	R_int = 0.032
8471 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.038	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.079	Δρ_max = 0.17 e Å⁻³
S = 0.97	Δρ_min = −0.15 e Å⁻³
3325 reflections	Absolute structure: Flack (1983), 1392 Friedel pairs
242 parameters	Absolute structure parameter: −0.02 (6)
0 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	−0.18920 (8)	0.39038 (5)	0.85472 (3)	0.0597 (2)
O1	0.1184 (2)	0.26483 (14)	0.84059 (11)	0.0792 (6)
O2	0.39800 (19)	1.08493 (11)	0.95249 (8)	0.0469 (4)
O3	0.6176 (2)	1.00534 (15)	1.00740 (9)	0.0630 (5)
C1	0.3598 (3)	0.50564 (17)	0.83239 (14)	0.0493 (7)
H1A	0.4714	0.5283	0.8150	0.059*
H1B	0.3671	0.5025	0.8826	0.059*
C2	0.3202 (3)	0.39468 (18)	0.80438 (14)	0.0568 (7)
H2A	0.3219	0.3961	0.7541	0.068*
H2B	0.4088	0.3458	0.8198	0.068*
C3	0.1487 (3)	0.35718 (19)	0.82862 (13)	0.0521 (7)
C4	0.0152 (3)	0.43994 (17)	0.83408 (11)	0.0392 (6)
C5	0.0422 (3)	0.54305 (17)	0.82283 (12)	0.0386 (6)
C6	−0.1033 (3)	0.62146 (17)	0.81864 (13)	0.0486 (6)
H6A	−0.2112	0.5863	0.8298	0.058*
H6B	−0.1118	0.6483	0.7716	0.058*
C7	−0.0757 (3)	0.71354 (17)	0.86839 (14)	0.0471 (6)
H7A	−0.1674	0.7650	0.8620	0.057*
H7B	−0.0820	0.6878	0.9157	0.057*
C8	0.0979 (2)	0.76714 (16)	0.85698 (12)	0.0341 (5)
H8	0.101 (3)	0.7987 (16)	0.8113 (11)	0.041*
C9	0.2445 (2)	0.68539 (16)	0.86173 (12)	0.0343 (5)
H9	0.240 (2)	0.6573 (16)	0.9119 (11)	0.041*
C10	0.2233 (2)	0.58776 (17)	0.81189 (11)	0.0368 (5)
C11	0.4216 (3)	0.73900 (17)	0.85446 (14)	0.0517 (7)
H11A	0.4337	0.7654	0.8075	0.062*
H11B	0.5112	0.6865	0.8619	0.062*
C12	0.4487 (3)	0.83096 (17)	0.90544 (14)	0.0490 (7)
H12A	0.4536	0.8035	0.9524	0.059*
H12B	0.5581	0.8653	0.8956	0.059*
C13	0.3036 (3)	0.91174 (16)	0.90011 (10)	0.0342 (5)
C14	0.1318 (3)	0.85315 (16)	0.91032 (12)	0.0354 (5)
H14	0.140 (3)	0.8154 (16)	0.9553 (12)	0.043*
C15	0.0001 (3)	0.94195 (17)	0.92036 (15)	0.0553 (7)
H15A	−0.0970	0.9178	0.9480	0.066*
H15B	−0.0425	0.9672	0.8760	0.066*
C16	0.1004 (3)	1.02920 (19)	0.95832 (15)	0.0545 (7)
H16A	0.0902	1.0960	0.9339	0.065*
H16B	0.0569	1.0382	1.0051	0.065*
C17	0.2886 (3)	0.99196 (17)	0.95951 (12)	0.0395 (5)
H17	0.325 (3)	0.9551 (17)	1.0049 (11)	0.047*
C18	0.3114 (4)	0.97189 (19)	0.83157 (12)	0.0572 (7)
H18A	0.2194	1.0228	0.8299	0.086*
H18B	0.2992	0.9230	0.7938	0.086*
H18C	0.4203	1.0077	0.8279	0.086*
C19	0.2448 (3)	0.6192 (2)	0.73547 (11)	0.0513 (7)
H19A	0.2299	0.5579	0.7067	0.077*
H19B	0.3582	0.6480	0.7284	0.077*
H19C	0.1597	0.6714	0.7235	0.077*
C20	0.5581 (3)	1.0808 (2)	0.97850 (13)	0.0477 (6)
C21	0.6504 (4)	1.1833 (2)	0.96711 (16)	0.0741 (9)
H21A	0.7083	1.2039	1.0091	0.111*
H21B	0.5685	1.2370	0.9543	0.111*
H21C	0.7337	1.1750	0.9306	0.111*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0606 (4)	0.0525 (4)	0.0660 (4)	−0.0228 (3)	0.0059 (3)	0.0004 (3)
O1	0.0913 (14)	0.0317 (10)	0.1147 (17)	−0.0053 (9)	−0.0191 (12)	0.0070 (11)
O2	0.0526 (10)	0.0304 (9)	0.0577 (10)	−0.0054 (8)	−0.0080 (8)	−0.0005 (8)
O3	0.0560 (11)	0.0604 (12)	0.0725 (13)	0.0045 (10)	−0.0090 (9)	0.0027 (10)
C1	0.0381 (13)	0.0344 (13)	0.0755 (18)	0.0063 (10)	0.0005 (11)	−0.0100 (13)
C2	0.0511 (14)	0.0368 (13)	0.0826 (19)	0.0094 (13)	−0.0048 (14)	−0.0104 (14)
C3	0.0690 (18)	0.0332 (15)	0.0541 (16)	−0.0028 (12)	−0.0187 (13)	−0.0016 (12)
C4	0.0418 (13)	0.0367 (14)	0.0392 (14)	−0.0070 (11)	−0.0041 (11)	−0.0010 (11)
C5	0.0404 (13)	0.0350 (13)	0.0403 (14)	−0.0021 (10)	−0.0017 (10)	−0.0045 (11)
C6	0.0339 (13)	0.0388 (13)	0.0732 (17)	−0.0040 (11)	−0.0038 (11)	−0.0058 (13)
C7	0.0307 (12)	0.0381 (13)	0.0725 (18)	0.0016 (10)	0.0041 (11)	−0.0075 (13)
C8	0.0298 (11)	0.0317 (12)	0.0407 (13)	0.0015 (9)	0.0011 (10)	0.0009 (11)
C9	0.0313 (11)	0.0316 (12)	0.0401 (13)	−0.0004 (9)	0.0021 (9)	−0.0031 (11)
C10	0.0351 (12)	0.0303 (12)	0.0449 (13)	−0.0025 (10)	0.0030 (9)	−0.0032 (11)
C11	0.0336 (12)	0.0412 (13)	0.0804 (19)	−0.0008 (10)	0.0076 (13)	−0.0216 (15)
C12	0.0325 (13)	0.0431 (14)	0.0714 (18)	−0.0014 (11)	−0.0006 (12)	−0.0172 (14)
C13	0.0355 (11)	0.0323 (12)	0.0348 (12)	−0.0028 (10)	0.0041 (10)	−0.0037 (10)
C14	0.0348 (13)	0.0325 (12)	0.0390 (13)	0.0012 (9)	0.0060 (10)	0.0002 (11)
C15	0.0391 (14)	0.0436 (15)	0.083 (2)	0.0051 (11)	0.0043 (13)	−0.0157 (14)
C16	0.0546 (16)	0.0423 (14)	0.0667 (17)	0.0055 (12)	0.0074 (14)	−0.0140 (14)
C17	0.0456 (14)	0.0302 (12)	0.0426 (14)	−0.0028 (11)	0.0017 (11)	−0.0030 (11)
C18	0.0751 (17)	0.0528 (15)	0.0436 (14)	−0.0181 (14)	0.0089 (14)	0.0012 (12)
C19	0.0582 (15)	0.0452 (16)	0.0506 (15)	−0.0037 (12)	0.0074 (11)	−0.0088 (13)
C20	0.0523 (16)	0.0449 (16)	0.0460 (15)	−0.0017 (13)	0.0035 (12)	−0.0119 (13)
C21	0.073 (2)	0.0543 (17)	0.095 (2)	−0.0212 (15)	−0.0063 (17)	−0.0127 (16)

Geometric parameters (Å, º) top

Cl1—C4	1.747 (2)	C11—C12	1.536 (3)
O1—C3	1.212 (3)	C11—H11A	0.9700
O2—C20	1.338 (3)	C11—H11B	0.9700
O2—C17	1.454 (3)	C12—C13	1.521 (3)
O3—C20	1.196 (3)	C12—H12A	0.9700
C1—C2	1.533 (3)	C12—H12B	0.9700
C1—C10	1.532 (3)	C13—C18	1.525 (3)
C1—H1A	0.9700	C13—C17	1.533 (3)
C1—H1B	0.9700	C13—C14	1.534 (3)
C2—C3	1.485 (4)	C14—C15	1.528 (3)
C2—H2A	0.9700	C14—H14	0.99 (2)
C2—H2B	0.9700	C15—C16	1.534 (3)
C3—C4	1.473 (3)	C15—H15A	0.9700
C4—C5	1.337 (3)	C15—H15B	0.9700
C5—C6	1.502 (3)	C16—C17	1.531 (3)
C5—C10	1.526 (3)	C16—H16A	0.9700
C6—C7	1.522 (3)	C16—H16B	0.9700
C6—H6A	0.9700	C17—H17	1.03 (2)
C6—H6B	0.9700	C18—H18A	0.9600
C7—C8	1.521 (3)	C18—H18B	0.9600
C7—H7A	0.9700	C18—H18C	0.9600
C7—H7B	0.9700	C19—H19A	0.9600
C8—C14	1.519 (3)	C19—H19B	0.9600
C8—C9	1.537 (3)	C19—H19C	0.9600
C8—H8	0.97 (2)	C20—C21	1.496 (3)
C9—C11	1.535 (3)	C21—H21A	0.9600
C9—C10	1.572 (3)	C21—H21B	0.9600
C9—H9	1.03 (2)	C21—H21C	0.9600
C10—C19	1.535 (3)

C20—O2—C17	118.21 (18)	C13—C12—C11	111.29 (19)
C2—C1—C10	112.97 (19)	C13—C12—H12A	109.4
C2—C1—H1A	109.0	C11—C12—H12A	109.4
C10—C1—H1A	109.0	C13—C12—H12B	109.4
C2—C1—H1B	109.0	C11—C12—H12B	109.4
C10—C1—H1B	109.0	H12A—C12—H12B	108.0
H1A—C1—H1B	107.8	C12—C13—C18	111.31 (18)
C3—C2—C1	111.1 (2)	C12—C13—C17	116.67 (18)
C3—C2—H2A	109.4	C18—C13—C17	108.70 (18)
C1—C2—H2A	109.4	C12—C13—C14	107.93 (16)
C3—C2—H2B	109.4	C18—C13—C14	112.67 (19)
C1—C2—H2B	109.4	C17—C13—C14	99.06 (16)
H2A—C2—H2B	108.0	C8—C14—C15	119.71 (19)
O1—C3—C4	122.3 (2)	C8—C14—C13	114.07 (16)
O1—C3—C2	122.6 (2)	C15—C14—C13	103.92 (17)
C4—C3—C2	115.0 (2)	C8—C14—H14	105.0 (12)
C5—C4—C3	124.8 (2)	C15—C14—H14	106.5 (12)
C5—C4—Cl1	121.81 (18)	C13—C14—H14	106.8 (12)
C3—C4—Cl1	113.38 (16)	C14—C15—C16	104.47 (19)
C4—C5—C6	122.3 (2)	C14—C15—H15A	110.9
C4—C5—C10	121.8 (2)	C16—C15—H15A	110.9
C6—C5—C10	115.94 (18)	C14—C15—H15B	110.9
C5—C6—C7	111.39 (18)	C16—C15—H15B	110.9
C5—C6—H6A	109.4	H15A—C15—H15B	108.9
C7—C6—H6A	109.4	C17—C16—C15	105.55 (18)
C5—C6—H6B	109.4	C17—C16—H16A	110.6
C7—C6—H6B	109.4	C15—C16—H16A	110.6
H6A—C6—H6B	108.0	C17—C16—H16B	110.6
C8—C7—C6	111.90 (19)	C15—C16—H16B	110.6
C8—C7—H7A	109.2	H16A—C16—H16B	108.8
C6—C7—H7A	109.2	O2—C17—C16	107.73 (18)
C8—C7—H7B	109.2	O2—C17—C13	114.86 (17)
C6—C7—H7B	109.2	C16—C17—C13	105.30 (19)
H7A—C7—H7B	107.9	O2—C17—H17	106.4 (12)
C14—C8—C7	111.91 (18)	C16—C17—H17	114.5 (12)
C14—C8—C9	108.23 (17)	C13—C17—H17	108.3 (11)
C7—C8—C9	110.17 (17)	C13—C18—H18A	109.5
C14—C8—H8	108.5 (12)	C13—C18—H18B	109.5
C7—C8—H8	109.9 (12)	H18A—C18—H18B	109.5
C9—C8—H8	108.1 (12)	C13—C18—H18C	109.5
C11—C9—C8	110.94 (17)	H18A—C18—H18C	109.5
C11—C9—C10	112.56 (17)	H18B—C18—H18C	109.5
C8—C9—C10	114.42 (17)	C10—C19—H19A	109.5
C11—C9—H9	105.5 (11)	C10—C19—H19B	109.5
C8—C9—H9	105.2 (11)	H19A—C19—H19B	109.5
C10—C9—H9	107.5 (11)	C10—C19—H19C	109.5
C5—C10—C1	110.32 (17)	H19A—C19—H19C	109.5
C5—C10—C19	109.15 (17)	H19B—C19—H19C	109.5
C1—C10—C19	110.36 (18)	O3—C20—O2	124.3 (2)
C5—C10—C9	107.58 (16)	O3—C20—C21	125.0 (2)
C1—C10—C9	107.54 (16)	O2—C20—C21	110.7 (2)
C19—C10—C9	111.85 (18)	C20—C21—H21A	109.5
C9—C11—C12	113.41 (19)	C20—C21—H21B	109.5
C9—C11—H11A	108.9	H21A—C21—H21B	109.5
C12—C11—H11A	108.9	C20—C21—H21C	109.5
C9—C11—H11B	108.9	H21A—C21—H21C	109.5
C12—C11—H11B	108.9	H21B—C21—H21C	109.5
H11A—C11—H11B	107.7

C10—C1—C2—C3	−57.7 (3)	C11—C9—C10—C19	−59.0 (2)
C1—C2—C3—O1	−146.8 (2)	C8—C9—C10—C19	68.8 (2)
C1—C2—C3—C4	35.8 (3)	C8—C9—C11—C12	53.4 (3)
O1—C3—C4—C5	178.6 (2)	C10—C9—C11—C12	−176.93 (19)
C2—C3—C4—C5	−4.0 (3)	C9—C11—C12—C13	−54.1 (3)
O1—C3—C4—Cl1	−3.1 (3)	C11—C12—C13—C18	−69.5 (2)
C2—C3—C4—Cl1	174.23 (17)	C11—C12—C13—C17	164.98 (19)
C3—C4—C5—C6	170.6 (2)	C11—C12—C13—C14	54.6 (2)
Cl1—C4—C5—C6	−7.5 (3)	C7—C8—C14—C15	−54.6 (3)
C3—C4—C5—C10	−8.1 (4)	C9—C8—C14—C15	−176.23 (19)
Cl1—C4—C5—C10	173.84 (16)	C7—C8—C14—C13	−178.57 (18)
C4—C5—C6—C7	126.6 (2)	C9—C8—C14—C13	59.8 (2)
C10—C5—C6—C7	−54.7 (3)	C12—C13—C14—C8	−60.2 (2)
C5—C6—C7—C8	54.8 (3)	C18—C13—C14—C8	63.1 (2)
C6—C7—C8—C14	−175.36 (19)	C17—C13—C14—C8	177.88 (18)
C6—C7—C8—C9	−54.9 (3)	C12—C13—C14—C15	167.8 (2)
C14—C8—C9—C11	−54.1 (2)	C18—C13—C14—C15	−68.9 (2)
C7—C8—C9—C11	−176.8 (2)	C17—C13—C14—C15	45.8 (2)
C14—C8—C9—C10	177.19 (17)	C8—C14—C15—C16	−162.1 (2)
C7—C8—C9—C10	54.5 (3)	C13—C14—C15—C16	−33.5 (2)
C4—C5—C10—C1	−13.1 (3)	C14—C15—C16—C17	7.2 (3)
C6—C5—C10—C1	168.1 (2)	C20—O2—C17—C16	154.1 (2)
C4—C5—C10—C19	108.3 (2)	C20—O2—C17—C13	−88.9 (2)
C6—C5—C10—C19	−70.4 (2)	C15—C16—C17—O2	144.7 (2)
C4—C5—C10—C9	−130.1 (2)	C15—C16—C17—C13	21.7 (3)
C6—C5—C10—C9	51.1 (2)	C12—C13—C17—O2	85.0 (2)
C2—C1—C10—C5	45.1 (3)	C18—C13—C17—O2	−41.8 (2)
C2—C1—C10—C19	−75.5 (2)	C14—C13—C17—O2	−159.60 (18)
C2—C1—C10—C9	162.20 (19)	C12—C13—C17—C16	−156.7 (2)
C11—C9—C10—C5	−178.85 (19)	C18—C13—C17—C16	76.5 (2)
C8—C9—C10—C5	−51.0 (2)	C14—C13—C17—C16	−41.3 (2)
C11—C9—C10—C1	62.3 (2)	C17—O2—C20—O3	−0.1 (3)
C8—C9—C10—C1	−169.83 (18)	C17—O2—C20—C21	−179.48 (19)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6B···O1ⁱ	0.97	2.62	3.565 (3)	166

Symmetry code: (i) −x, y+1/2, −z+3/2.

Experimental details

Crystal data
Chemical formula	C₂₁H₂₉ClO₃
M_r	364.89
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	295
a, b, c (Å)	7.740 (1), 12.631 (2), 19.275 (2)
V (Å³)	1884.4 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.22
Crystal size (mm)	0.26 × 0.11 × 0.10

Data collection
Diffractometer	Bruker SMART APEX CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)
T_min, T_max	0.945, 0.978
No. of measured, independent and observed [I > 2σ(I)] reflections	8471, 3325, 2586
R_int	0.032
(sin θ/λ)_max (Å⁻¹)	0.597

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.038, 0.079, 0.97
No. of reflections	3325
No. of parameters	242
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.17, −0.15
Absolute structure	Flack (1983), 1392 Friedel pairs
Absolute structure parameter	−0.02 (6)

Computer programs: SMART (Bruker, 2003), SAINT (Bruker, 2003), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), SHELXTL/NT (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6B···O1ⁱ	0.97	2.62	3.565 (3)	166.0

Symmetry code: (i) −x, y+1/2, −z+3/2.

Acknowledgements

Samples of the title compound were kindly provided by Steroid SPA (Via Spagna 156, 20093 Cologno Monzese, Milano, Italy).

References

Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19. CrossRef Web of Science 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
Böcskei, Z., Gérczei, T., Bodor, A., Schwartz, R. & Náray-Szabó, G. (1996). Acta Cryst. C52, 2899–2903. CSD CrossRef Web of Science IUCr Journals Google Scholar
Bruker (2003). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Camerino, B., Patelli, B. & Vercellone, A. (1956). J. Am. Chem. Soc. 78, 3540–3541. CrossRef CAS Web of Science Google Scholar
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358. CrossRef CAS Web of Science Google Scholar
Duax, W. L., Cooper, A. & Norton, D. A. (1971). Acta Cryst. B27, 1–6. CSD CrossRef CAS IUCr Journals Web of Science Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Julian Laboratories Inc. Illinois (1960). US Patent 2933510. Google Scholar
Sheldrick, G. M. (1996). 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
Società Farmaceutici Italia (1960). US Patent 2953582. Google Scholar
Sweetman, S. C. (2009). Editor. Martindale: The Complete Drug Reference, 36th ed. London: The Pharmaceutical Press. Google Scholar
Verma, R., Jasrotia, D. & Bhat, M. (2006). J. Chem. Crystallogr. 36, 283–287. Web of Science CSD CrossRef CAS Google Scholar