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Ezetimibe {systematic name: (3R,4S)-1-(4-fluoro­phen­yl)-3-[(3S)-3-(4-fluoro­phen­yl)-3-hy­droxy­prop­yl]-4-(4-hy­droxy­phen­yl)azetidin-2-one}, C24H21F2NO3, is used to lower cholesterol levels by inhibiting cholesterol resorption in the human intestine. The crystal structure of ezetimibe anhydrate was solved from laboratory powder diffraction data by means of real-space methods using the program DASH [David et al. (2006). J. Appl. Cryst. 39, 910-915]. Subsequent Rietveld refinement with TOPAS Academic [Coelho (2007). TOPAS Academic User Manual. Version 4.1. Coelho Software, Brisbane, Australia] led to a final Rwp value of 8.19% at 1.75 Å resolution. The compound crystallizes in the space group P212121 with one mol­ecule in the asymmetric unit. The mol­ecules are closely packed and two inter­molecular hydrogen bonds form an extended hydrogen-bond architecture.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270110019190/gt3018sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270110019190/gt3018Isup2.hkl
Contains datablock I

rtv

Rietveld powder data file (CIF format) https://doi.org/10.1107/S0108270110019190/gt3018Isup3.rtv
Contains datablock I

CCDC reference: 786811

Computing details top

Data collection: Stoe WINXPOW (Stoe & Cie, 1988); cell refinement: TOPAS Academic (Coelho, 2007); data reduction: DASH (David et al., 2006); program(s) used to solve structure: DASH (David et al., 2006); program(s) used to refine structure: TOPAS Academic (Coelho, 2007); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: publCIF (Westrip, 2010).

(3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)- 3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one top
Crystal data top
C24H21F2NO3F(000) = 856
Mr = 409.42Dx = 1.347 Mg m3
Orthorhombic, P212121Cu Kα1 radiation, λ = 1.5406 Å
Hall symbol: P 2ac 2abµ = 0.84 mm1
a = 5.94606 (19) ÅT = 293 K
b = 15.8898 (5) ÅParticle morphology: no specific habit
c = 21.3765 (6) Åwhite
V = 2019.69 (11) Å3cylinder, 10 × 0.7 mm
Z = 4Specimen preparation: Prepared at 293 K
Data collection top
Stoe Stadi-P
diffractometer with linear position-sensitive detector
Data collection mode: transmission
Radiation source: sealed X-ray tubeScan method: step
Primary focussing, Ge 111 monochromator2θmin = 3°, 2θmax = 69.99°, 2θstep = 0.01°
Specimen mounting: glass capillary
Refinement top
Refinement on Inet196 parameters
Least-squares matrix: full with fixed elements per cycle208 restraints
Rp = 0.0790 constraints
Rwp = 0.082All H-atom parameters refined
Rexp = 0.071Weighting scheme based on measured s.u.'s w = 1/σ[Yobs)2
RBragg = 1.094(Δ/σ)max = 0.001
6700 data pointsBackground function: Bayesian high-pass filter with 20 terms
Excluded region(s): nonePreferred orientation correction: none
Profile function: modified Thompson-Cox-Hastings pseudo-Voigt (Young, 1993)
Special details top

Experimental. specimen was rotated

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.8376 (7)0.7622 (3)0.78693 (17)0.056 (1)
C110.8616 (6)0.7090 (2)0.73652 (14)0.056 (1)
C120.6960 (6)0.7035 (2)0.69024 (16)0.056 (1)
H120.565 (2)0.7401 (10)0.6945 (6)0.067 (2)
C130.7249 (6)0.6467 (2)0.63929 (14)0.056 (1)
H130.626 (2)0.6396 (8)0.6071 (5)0.067 (2)
C140.9080 (6)0.6006 (2)0.63697 (14)0.056 (1)
F140.9388 (7)0.5468 (2)0.59029 (19)0.087 (3)
C151.0698 (6)0.6045 (2)0.68028 (16)0.056 (1)
H151.197 (2)0.5687 (9)0.6750 (6)0.067 (2)
C161.0500 (6)0.6600 (2)0.73206 (14)0.056 (1)
H161.154 (2)0.6641 (10)0.7616 (6)0.067 (2)
C20.9265 (8)0.7650 (3)0.8447 (2)0.056 (1)
O21.0908 (9)0.7290 (4)0.8662 (2)0.056 (1)
C30.7580 (7)0.8320 (3)0.86934 (17)0.056 (1)
H30.816 (2)0.8915 (9)0.8726 (6)0.067 (2)
C310.6498 (6)0.8061 (2)0.93088 (18)0.056 (1)
H31b0.769 (3)0.7934 (9)0.9600 (7)0.067 (2)
H31a0.565 (3)0.7570 (8)0.9241 (5)0.067 (2)
C320.5114 (6)0.8750 (2)0.95722 (17)0.056 (1)
H32a0.442 (2)0.9055 (8)0.9234 (6)0.067 (2)
H32b0.402 (3)0.8518 (8)0.9834 (7)0.067 (2)
C330.6517 (6)0.9325 (2)0.99593 (16)0.056 (1)
H33a0.789 (2)0.9477 (10)0.9727 (6)0.067 (2)
H33b0.638 (2)0.8544 (9)1.0767 (6)0.067 (2)
C340.5467 (6)1.0118 (2)1.01939 (15)0.056 (1)
C350.6513 (6)1.0895 (2)1.00967 (12)0.056 (1)
H350.793 (2)1.0912 (9)0.9856 (6)0.067 (2)
C360.5501 (6)1.1644 (2)1.03423 (14)0.056 (1)
H360.613 (3)1.2194 (8)1.0287 (6)0.067 (2)
C370.3510 (6)1.1575 (2)1.06703 (13)0.056 (1)
F370.2580 (7)1.2276 (3)1.09075 (16)0.087 (3)
C380.2490 (5)1.0826 (2)1.07628 (15)0.056 (1)
H380.117 (2)1.0787 (9)1.0978 (6)0.067 (2)
C390.3468 (6)1.0104 (2)1.05259 (14)0.056 (1)
H390.273 (2)0.9611 (9)1.0596 (5)0.067 (2)
O330.7337 (7)0.8871 (3)1.0496 (2)0.056 (1)
C40.6449 (6)0.8157 (2)0.80320 (16)0.056 (1)
H40.508 (2)0.7833 (9)0.8087 (6)0.067 (2)
C410.6082 (6)0.8903 (2)0.76234 (16)0.056 (1)
C420.4144 (6)0.9347 (2)0.76716 (16)0.056 (1)
H420.306 (2)0.9188 (9)0.7953 (6)0.067 (2)
C430.3687 (5)1.0031 (2)0.73212 (15)0.056 (1)
H430.242 (3)1.0287 (9)0.7376 (6)0.067 (2)
C440.5156 (7)1.0332 (2)0.68926 (16)0.056 (1)
H440.511 (6)1.1066 (8)0.6092 (6)0.067 (2)
O440.4729 (9)1.1015 (3)0.65419 (17)0.056 (1)
H450.807 (3)1.0136 (9)0.6529 (6)0.067 (2)
C450.7119 (6)0.9916 (2)0.68256 (16)0.056 (1)
C460.7626 (6)0.9189 (2)0.71895 (15)0.056 (1)
H460.906 (2)0.8889 (9)0.7132 (6)0.067 (2)
Geometric parameters (Å, º) top
N1—C111.378 (5)C33—O331.439 (6)
N1—C21.343 (6)H33b—O330.97 (1)
N1—C41.468 (6)C34—C351.398 (5)
C11—C121.399 (5)C34—C391.384 (5)
C11—C161.367 (5)C35—H350.99 (1)
C12—H120.97 (1)C35—C361.434 (5)
C12—C131.425 (5)C36—H360.96 (1)
C13—H130.91 (1)C36—C371.380 (5)
C13—C141.313 (5)C37—F371.343 (5)
C14—F141.327 (5)C37—C381.350 (5)
C14—C151.337 (5)C38—H380.91 (1)
C15—H150.95 (1)C38—C391.383 (5)
C15—C161.420 (5)C39—H390.91 (1)
C16—H160.89 (1)C4—H40.97 (1)
C2—O21.222 (7)C4—C411.488 (5)
C2—C31.554 (6)C41—C421.355 (5)
C3—H31.01 (1)C41—C461.382 (5)
C3—C311.521 (5)C42—H420.92 (1)
C3—C41.587 (5)C42—C431.347 (5)
C31—H31b0.96 (1)C43—H430.87 (2)
C31—H31a0.94 (1)C43—C441.354 (5)
C31—C321.481 (5)C44—O441.343 (5)
C32—H32a0.97 (1)C44—C451.349 (5)
C32—H32b0.93 (1)H44—O440.99 (1)
C32—C331.489 (5)H45—C450.92 (1)
C33—H33a0.99 (1)C45—C461.426 (5)
C33—C341.493 (5)C46—H460.98 (1)
C11—N1—C2134.3 (4)H33a—C33—O33104.1 (9)
C11—N1—C4128.4 (3)C34—C33—O33107.3 (3)
C2—N1—C494.0 (3)C33—C34—C35120.6 (3)
N1—C11—C12121.2 (3)C33—C34—C39121.2 (3)
N1—C11—C16119.3 (3)C35—C34—C39118.2 (3)
C12—C11—C16119.5 (3)C34—C35—H35118.8 (9)
C11—C12—H12117.2 (9)C34—C35—C36119.5 (3)
C11—C12—C13119.7 (3)H35—C35—C36121.7 (9)
H12—C12—C13123.1 (9)C35—C36—H36123.3 (9)
C12—C13—H13125.1 (8)C35—C36—C37118.7 (3)
C12—C13—C14118.9 (3)H36—C36—C37118.0 (9)
H13—C13—C14116.0 (8)C36—C37—F37118.6 (3)
C13—C14—F14120.2 (3)C36—C37—C38122.0 (3)
C13—C14—C15123.0 (3)F37—C37—C38119.4 (3)
F14—C14—C15116.9 (3)C37—C38—H38121.4 (9)
C14—C15—H15117.3 (9)C37—C38—C39119.3 (3)
C14—C15—C16120.6 (3)H38—C38—C39119.4 (9)
H15—C15—C16122.0 (9)C34—C39—C38122.4 (3)
C11—C16—C15118.4 (3)C34—C39—H39120.7 (9)
C11—C16—H16119 (1)C38—C39—H39116.9 (9)
C15—C16—H16123 (1)C33—O33—H33b123.2 (9)
N1—C2—O2130.2 (5)N1—C4—C388.6 (3)
N1—C2—C394.6 (4)N1—C4—H4112.1 (8)
O2—C2—C3135.1 (5)N1—C4—C41115.9 (3)
C2—C3—H3116.4 (8)C3—C4—H4109.5 (8)
C2—C3—C31112.4 (3)C3—C4—C41117.1 (3)
C2—C3—C481.9 (3)H4—C4—C41111.8 (8)
H3—C3—C31109.8 (8)C4—C41—C42119.7 (3)
H3—C3—C4111.0 (8)C4—C41—C46123.9 (3)
C31—C3—C4123.2 (3)C42—C41—C46116.4 (3)
C3—C31—H31b107.7 (9)C41—C42—H42120.3 (9)
C3—C31—H31a108.6 (9)C41—C42—C43123.3 (3)
C3—C31—C32111.3 (3)H42—C42—C43116.4 (9)
H31b—C31—H31a109 (1)C42—C43—H43119 (1)
H31b—C31—C32108.5 (9)C42—C43—C44122.1 (3)
H31a—C31—C32111.8 (9)H43—C43—C44119 (1)
C31—C32—H32a109.0 (8)C43—C44—O44122.8 (4)
C31—C32—H32b108.9 (9)C43—C44—C45117.2 (3)
C31—C32—C33110.7 (3)O44—C44—C45120.0 (4)
H32a—C32—H32b110 (1)C44—O44—H44124 (1)
H32a—C32—C33110.5 (8)C44—C45—H45114.9 (9)
H32b—C32—C33107.4 (9)C44—C45—C46121.5 (3)
C32—C33—H33a109.5 (9)H45—C45—C46123.6 (9)
C32—C33—C34118.1 (3)C41—C46—C45119.5 (3)
C32—C33—O33108.9 (3)C41—C46—H46120.0 (8)
H33a—C33—C34108.1 (9)C45—C46—H46120.5 (8)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O44—H44···O33i0.99 (1)1.99 (3)2.842 (6)143 (2)
O33—H33b···O2ii0.97 (1)1.82 (1)2.715 (7)152 (1)
Symmetry codes: (i) x+3/2, y+2, z1/2; (ii) x1/2, y+3/2, z+2.
Comparison of selected torsions (°) of (I) anhydrate and (I).H2O. top
Torsion(I)(I).H2O
C3—C31—C32—C33-86.6 (4)-167.1 (3)
C34—C33—C32—C31172.2 (3)167.8 (2)
C35—C34—C33—C32-128.2 (4)-63.3 (4)
O33—C33—C32—C31-65.2 (4)-68.9 (3)
N1—C4—C41—C46-11.8 (5)-23.9 (4)
C31—C3—C4—C41123.6 (4)120.4 (3)
C4—N1—C11—C123.8 (6)6.4 (4)
 

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