Degradation of atorvastatin: (1R,2S,4S,5S)-4-(4-fluoro­phen­yl)-2-hydro­peroxy-4-hydr­oxy-2-isopropyl-N,5-diphenyl-3,6-dioxabicyclo­[3.1.0]hexane-1-carboxamide

Ashfaq, M.; Tahir, M.N.; Khan, I.U.; Iqbal, M.S.; Arshad, M.N.

doi:10.1107/S1600536808022265

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 64| Part 8| August 2008| Page o1548

doi:10.1107/S1600536808022265

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Degradation of atorvastatin: (1R,2S,4S,5S)-4-(4-fluorophenyl)-2-hydroperoxy-4-hydroxy-2-isopropyl-N,5-diphenyl-3,6-dioxabicyclo[3.1.0]hexane-1-carboxamide

Muhammad Ashfaq,^a Muhammad Nawaz Tahir,^b ^* Islam Ullah Khan,^a Mohammad S. Iqbal ^a and Muhammad Nadeem Arshad ^a

^aDepartment of Chemistry, Government College University, Lahore, Pakistan, and ^bDepartment of Physics, University of Sargodha, Sargodha, Pakistan
^*Correspondence e-mail: dmntahir_uos@yahoo.com

(Received 18 June 2008; accepted 16 July 2008; online 19 July 2008)

The degradation of atorvastatin calcium in methanol and hydrogen peroxide results in the crystallization of the title compound, C₂₆H₂₄FNO₆, which shows several differences compared with the starting compound. In the crystal structure of the title compound, intra- and intermolecular hydrogen bonding is found.

Related literature

For related literature, see: Cremer & Pople (1975 ); Rouleau (2005 ); United States Pharmacopeia (2007 ).

Experimental

Crystal data

C₂₆H₂₄FNO₆
M_r = 465.46
Monoclinic, P 2₁ /n
a = 11.7560 (6) Å
b = 11.7489 (6) Å
c = 17.0889 (9) Å
β = 94.438 (2)°
V = 2353.2 (2) Å³
Z = 4
Mo Kα radiation radiation
μ = 0.10 mm⁻¹
T = 296 (2) K
0.25 × 0.18 × 0.15 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ) T_min = 0.975, T_max = 0.980
14754 measured reflections
5340 independent reflections
3008 reflections with I > 2σ(I)
R_int = 0.040

Refinement

R[F² > 2σ(F²)] = 0.049
wR(F²) = 0.136
S = 1.02
5340 reflections
318 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.34 e Å⁻³
Δρ_min = −0.28 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O3	0.86 (2)	2.36 (2)	2.780 (2)	110.8 (17)
N1—H1⋯O2ⁱ	0.86 (2)	2.37 (2)	3.216 (2)	168.0 (18)
O2—H2⋯O5	0.84 (2)	2.15 (2)	2.920 (2)	152 (2)
O2—H2⋯O3ⁱⁱ	0.84 (2)	2.35 (2)	2.8188 (18)	116.1 (18)
O5—H5⋯O6	0.82	1.99	2.655 (2)	138
Symmetry codes: (i) $[-x+{\script{3\over 2}}, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) $[-x+{\script{3\over 2}}, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Data collection: APEX2 (Bruker, 2007 ); cell refinement: APEX2; data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ) and PLATON (Spek, 2003 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ) and PLATON.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808022265/nc2108sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808022265/nc2108Isup2.hkl

checkCIF report

Comment top

Atorvastatin calcium is widly used as synthetic lipid-lowering agent (Rouleau, 2005). The medicinal organic compounds are affected by the environment in which they are stored and produce degradation products through reactions with moisture (humidity) and oxygen in air (oxidation) or due to thermal shocks. Thus, all the drug substances are given an expiration date which is the time at which 10% of the initial amount of a drug is transformed to various degradation products (United States Pharmacopeia, 2007). Thus it is a standard practice to study the stability profile of a drug substance under stress. In order to simulate the air oxidation under accelerated conditions the products are subjected to the reaction with hydrogen peroxide. The purpose of this study was to see the reaction of atorvastatin calcium towards hydrogen peroxide. In this example, the title compound crystallized after the reaction at ambient temperature.

In the structure of the title compound, the central five-membered ring (O1/C1–C4) is in an envelope conformation, with the C1–C4 atoms in the plane (Fig. 1). The puckering parameters (Cremer & Pople, 1975) are Q = 0.9737 (16)Å, θ = 115.69 (10)° and ϕ = 0.10 (13)°. The dihedral angles between this ring and benzene rings C6–C11, C12–C17 and C18–C23 are 88.71 (11), 66.85 (11) and 64.39 (12)°, respectively. There is intramolecular O—H···O and N—H···O hydrogen bonding between N1 and O3, between O2 and O5 and between O5 and O6 (Fig. 1 and Table 1). In the crystal structure, the molecules are connected via intermolecular O—H···O and N—H···O hydrogen bonding (Table 1).

Related literature top

For related literature, see: Cremer & Pople (1975); Rouleau (2005); United States Pharmacopeia (2007).

Experimental top

Atorvastatin calcium (100 mg) was dissolved in methanol (25 ml) at room temperature. A separate solution (10 ml) of hydrogen peroxide (5%) was prepared in distilled water. Both the solutions were mixed togather and set aside for 2 months. The crystals suitable for x-ray diffraction of the title compound (I) were obtained by filteration.

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: APEX2 (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and PLATON (Spek, 2003); software used to prepare material for publication: WinGX (Farrugia, 1999) and PLATON (Spek, 2003).

Figures top

	Fig. 1. ORTEP drawing of the title compound, with the atom numbering scheme. The thermal ellipsoids are drawn at the 30% probability level. H-atoms are shown by small circles of arbitrary radii. The dashed lines shows intramolecular H-bonding.
	Fig. 2. The formation of the title compound.

(1R,2S,4S,5S)-4-(4-fluorophenyl)- 2-hydroperoxy-4-hydroxy-2-isopropyl-N,5-diphenyl-3,6- dioxabicyclo[3.1.0]hexane-1-carboxamide top

Crystal data top

C₂₆H₂₄FNO₆	F(000) = 976
M_r = 465.46	D_x = 1.314 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 5340 reflections
a = 11.7560 (6) Å	θ = 2.0–27.5°
b = 11.7489 (6) Å	µ = 0.10 mm⁻¹
c = 17.0889 (9) Å	T = 296 K
β = 94.438 (2)°	Prismatic, colorless
V = 2353.2 (2) Å³	0.25 × 0.18 × 0.15 mm
Z = 4

Data collection top

Bruker Kappa APEXII CCD diffractometer	5340 independent reflections
Radiation source: fine-focus sealed tube	3008 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.040
Detector resolution: 7.50 pixels mm^-1	θ_max = 27.5°, θ_min = 2.0°
ω scans	h = −15→14
Absorption correction: multi-scan (SADABS; Bruker, 2005)	k = −15→8
T_min = 0.975, T_max = 0.980	l = −22→21
14754 measured reflections

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)] = 0.049	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.136	w = 1/[σ²(F_o²) + (0.0541P)² + 0.5969P] where P = (F_o² + 2F_c²)/3
S = 1.02	(Δ/σ)_max < 0.001
5340 reflections	Δρ_max = 0.34 e Å⁻³
318 parameters	Δρ_min = −0.28 e Å⁻³
0 restraints	Extinction correction: emperical, Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0032 (7)

Crystal data top

C₂₆H₂₄FNO₆	V = 2353.2 (2) Å³
M_r = 465.46	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 11.7560 (6) Å	µ = 0.10 mm⁻¹
b = 11.7489 (6) Å	T = 296 K
c = 17.0889 (9) Å	0.25 × 0.18 × 0.15 mm
β = 94.438 (2)°

Data collection top

Bruker Kappa APEXII CCD diffractometer	5340 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2005)	3008 reflections with I > 2σ(I)
T_min = 0.975, T_max = 0.980	R_int = 0.040
14754 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.049	0 restraints
wR(F²) = 0.136	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	Δρ_max = 0.34 e Å⁻³
5340 reflections	Δρ_min = −0.28 e Å⁻³
318 parameters

Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

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
F1	0.7275 (2)	0.00876 (18)	−0.10244 (10)	0.1428 (12)
O1	0.91061 (11)	0.21012 (11)	0.21795 (7)	0.0426 (5)
O2	0.78009 (12)	0.35021 (11)	0.17484 (8)	0.0455 (5)
O3	0.75203 (11)	0.07280 (10)	0.26940 (7)	0.0383 (4)
O4	0.96555 (12)	0.28576 (11)	0.34067 (8)	0.0512 (5)
O5	0.88438 (14)	0.38004 (12)	0.33419 (9)	0.0591 (6)
O6	0.78216 (14)	0.25802 (13)	0.43917 (8)	0.0622 (6)
N1	0.70884 (15)	0.07964 (14)	0.42697 (10)	0.0428 (6)
C1	0.79736 (16)	0.23366 (15)	0.18667 (11)	0.0373 (6)
C2	0.72161 (16)	0.18934 (14)	0.24910 (11)	0.0361 (6)
C3	0.79830 (16)	0.16319 (15)	0.31885 (11)	0.0362 (6)
C4	0.91978 (17)	0.19004 (16)	0.30000 (11)	0.0398 (6)
C5	0.76193 (17)	0.17068 (16)	0.40107 (11)	0.0426 (7)
C6	0.66547 (17)	0.06482 (18)	0.50124 (11)	0.0430 (7)
C7	0.64405 (19)	−0.0442 (2)	0.52493 (13)	0.0545 (8)
C8	0.5989 (2)	−0.0630 (3)	0.59596 (16)	0.0742 (10)
C9	0.5747 (2)	0.0265 (3)	0.64262 (15)	0.0848 (13)
C10	0.5957 (3)	0.1338 (3)	0.61935 (17)	0.0905 (14)
C11	0.6417 (2)	0.1550 (2)	0.54889 (15)	0.0731 (10)
C12	0.60000 (17)	0.22332 (16)	0.24931 (12)	0.0432 (7)
C13	0.56860 (19)	0.31146 (18)	0.29682 (14)	0.0535 (8)
C14	0.4566 (2)	0.3464 (2)	0.29578 (17)	0.0691 (10)
C15	0.3765 (2)	0.2949 (2)	0.2464 (2)	0.0809 (13)
C16	0.4051 (2)	0.2077 (3)	0.1996 (2)	0.0851 (13)
C17	0.5172 (2)	0.1703 (2)	0.20123 (15)	0.0634 (9)
C18	0.77882 (17)	0.17385 (16)	0.10816 (11)	0.0417 (7)
C19	0.6918 (2)	0.2070 (2)	0.05454 (13)	0.0628 (9)
C20	0.6729 (3)	0.1504 (3)	−0.01611 (15)	0.0865 (13)
C21	0.7429 (3)	0.0629 (3)	−0.03176 (16)	0.0877 (13)
C22	0.8274 (3)	0.0266 (2)	0.01933 (17)	0.0858 (13)
C23	0.8452 (2)	0.08283 (19)	0.09060 (14)	0.0633 (9)
C24	1.00575 (18)	0.09376 (19)	0.31729 (13)	0.0483 (8)
C25	1.1220 (2)	0.1214 (2)	0.28961 (16)	0.0707 (10)
C26	1.0152 (2)	0.0571 (2)	0.40307 (14)	0.0725 (10)
H1	0.7025 (18)	0.0224 (18)	0.3959 (12)	0.0513*
H2	0.7978 (19)	0.3806 (18)	0.2186 (13)	0.0546*
H5	0.84238	0.37658	0.37026	0.0709*
H7	0.65998	−0.10545	0.49308	0.0653*
H8	0.58498	−0.13698	0.61205	0.0891*
H9	0.54382	0.01370	0.69032	0.1016*
H10	0.57890	0.19449	0.65141	0.1082*
H11	0.65640	0.22924	0.53375	0.0877*
H13	0.62383	0.34762	0.32991	0.0642*
H14	0.43608	0.40471	0.32866	0.0830*
H15	0.30121	0.31969	0.24457	0.0971*
H16	0.34924	0.17291	0.16623	0.1022*
H17	0.53617	0.10956	0.16989	0.0761*
H19	0.64536	0.26790	0.06595	0.0754*
H20	0.61343	0.17187	−0.05218	0.1038*
H22	0.87298	−0.03469	0.00730	0.1031*
H23	0.90295	0.05841	0.12698	0.0760*
H24	0.9756 (19)	0.0315 (18)	0.2877 (12)	0.0580*
H25A	1.17269	0.05848	0.30093	0.1061*
H25B	1.15192	0.18810	0.31628	0.1061*
H25C	1.11487	0.13507	0.23406	0.1061*
H26A	1.06946	−0.00373	0.41036	0.1087*
H26B	0.94205	0.03156	0.41737	0.1087*
H26C	1.03999	0.12047	0.43554	0.1087*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.231 (3)	0.1278 (16)	0.0649 (12)	−0.0243 (16)	−0.0177 (13)	−0.0448 (11)
O1	0.0387 (8)	0.0528 (8)	0.0357 (8)	−0.0054 (6)	−0.0016 (6)	0.0093 (6)
O2	0.0619 (10)	0.0324 (7)	0.0409 (8)	−0.0028 (6)	−0.0034 (7)	0.0037 (6)
O3	0.0471 (8)	0.0307 (6)	0.0361 (7)	−0.0042 (6)	−0.0036 (6)	0.0030 (5)
O4	0.0506 (9)	0.0456 (8)	0.0549 (9)	−0.0083 (7)	−0.0120 (7)	−0.0004 (7)
O5	0.0700 (11)	0.0434 (8)	0.0632 (11)	−0.0068 (8)	0.0008 (8)	−0.0020 (7)
O6	0.0906 (12)	0.0504 (9)	0.0464 (9)	−0.0176 (8)	0.0105 (8)	−0.0098 (7)
N1	0.0522 (11)	0.0422 (9)	0.0347 (10)	−0.0061 (8)	0.0080 (8)	−0.0016 (7)
C1	0.0396 (12)	0.0348 (10)	0.0362 (11)	−0.0016 (8)	−0.0044 (8)	0.0063 (8)
C2	0.0416 (12)	0.0293 (9)	0.0364 (11)	−0.0029 (8)	−0.0024 (8)	0.0022 (8)
C3	0.0414 (11)	0.0322 (9)	0.0339 (11)	−0.0048 (8)	−0.0032 (8)	0.0015 (8)
C4	0.0437 (12)	0.0412 (10)	0.0329 (11)	−0.0068 (9)	−0.0064 (9)	0.0042 (8)
C5	0.0492 (12)	0.0423 (11)	0.0357 (11)	−0.0021 (9)	−0.0004 (9)	0.0002 (9)
C6	0.0379 (12)	0.0577 (12)	0.0334 (11)	−0.0021 (10)	0.0024 (9)	0.0001 (10)
C7	0.0486 (13)	0.0631 (14)	0.0525 (14)	0.0022 (11)	0.0090 (11)	0.0138 (11)
C8	0.0561 (16)	0.103 (2)	0.0640 (17)	−0.0041 (14)	0.0080 (13)	0.0336 (16)
C9	0.0597 (18)	0.156 (3)	0.0398 (15)	−0.0171 (19)	0.0110 (12)	0.0042 (18)
C10	0.087 (2)	0.124 (3)	0.0645 (19)	−0.0228 (19)	0.0319 (16)	−0.0354 (18)
C11	0.0829 (19)	0.0770 (17)	0.0628 (17)	−0.0140 (14)	0.0274 (14)	−0.0194 (14)
C12	0.0416 (12)	0.0378 (10)	0.0497 (12)	−0.0045 (9)	−0.0002 (10)	0.0081 (9)
C13	0.0451 (14)	0.0472 (12)	0.0682 (16)	0.0003 (10)	0.0045 (11)	0.0015 (11)
C14	0.0549 (16)	0.0530 (14)	0.101 (2)	0.0052 (12)	0.0171 (15)	0.0081 (13)
C15	0.0405 (15)	0.0652 (17)	0.137 (3)	0.0015 (13)	0.0072 (16)	0.0209 (18)
C16	0.0458 (16)	0.0774 (19)	0.128 (3)	−0.0130 (14)	−0.0190 (16)	−0.0045 (18)
C17	0.0509 (15)	0.0561 (14)	0.0810 (18)	−0.0072 (12)	−0.0098 (12)	−0.0047 (12)
C18	0.0531 (13)	0.0367 (10)	0.0343 (11)	−0.0045 (9)	−0.0031 (9)	0.0058 (8)
C19	0.0784 (18)	0.0555 (14)	0.0507 (14)	0.0011 (12)	−0.0196 (12)	0.0020 (11)
C20	0.120 (3)	0.080 (2)	0.0526 (17)	−0.0065 (18)	−0.0373 (16)	−0.0018 (14)
C21	0.142 (3)	0.0704 (19)	0.0476 (16)	−0.0215 (19)	−0.0116 (18)	−0.0167 (14)
C22	0.126 (3)	0.0653 (17)	0.0657 (19)	0.0120 (17)	0.0044 (18)	−0.0192 (14)
C23	0.0869 (19)	0.0527 (13)	0.0489 (14)	0.0085 (13)	−0.0044 (12)	−0.0052 (11)
C24	0.0447 (13)	0.0498 (12)	0.0488 (14)	0.0012 (10)	−0.0073 (10)	0.0072 (10)
C25	0.0432 (14)	0.0843 (18)	0.0840 (19)	0.0059 (12)	0.0013 (13)	0.0167 (14)
C26	0.0714 (17)	0.0825 (18)	0.0613 (16)	0.0128 (14)	−0.0092 (13)	0.0265 (13)

Geometric parameters (Å, º) top

F1—C21	1.365 (3)	C15—C16	1.358 (4)
O1—C1	1.423 (2)	C16—C17	1.387 (3)
O1—C4	1.418 (2)	C18—C19	1.376 (3)
O2—C1	1.397 (2)	C18—C23	1.371 (3)
O3—C2	1.450 (2)	C19—C20	1.381 (4)
O3—C3	1.438 (2)	C20—C21	1.356 (5)
O4—O5	1.461 (2)	C21—C22	1.340 (5)
O4—C4	1.407 (2)	C22—C23	1.387 (4)
O6—C5	1.229 (2)	C24—C25	1.516 (3)
O2—H2	0.84 (2)	C24—C26	1.524 (3)
O5—H5	0.8200	C7—H7	0.9300
N1—C5	1.331 (3)	C8—H8	0.9300
N1—C6	1.415 (3)	C9—H9	0.9300
N1—H1	0.86 (2)	C10—H10	0.9300
C1—C18	1.515 (3)	C11—H11	0.9300
C1—C2	1.533 (3)	C13—H13	0.9300
C2—C3	1.470 (3)	C14—H14	0.9300
C2—C12	1.485 (3)	C15—H15	0.9300
C3—C4	1.521 (3)	C16—H16	0.9300
C3—C5	1.503 (3)	C17—H17	0.9300
C4—C24	1.530 (3)	C19—H19	0.9300
C6—C11	1.378 (3)	C20—H20	0.9300
C6—C7	1.373 (3)	C22—H22	0.9300
C7—C8	1.380 (3)	C23—H23	0.9300
C8—C9	1.363 (5)	C24—H24	0.94 (2)
C9—C10	1.350 (5)	C25—H25A	0.9600
C10—C11	1.380 (4)	C25—H25B	0.9600
C12—C17	1.374 (3)	C25—H25C	0.9600
C12—C13	1.384 (3)	C26—H26A	0.9600
C13—C14	1.378 (3)	C26—H26B	0.9600
C14—C15	1.357 (4)	C26—H26C	0.9600

C1—O1—C4	113.66 (14)	C18—C19—C20	120.5 (2)
C2—O3—C3	61.20 (11)	C19—C20—C21	118.6 (3)
O5—O4—C4	110.25 (14)	F1—C21—C20	119.1 (3)
C1—O2—H2	105.3 (14)	F1—C21—C22	118.0 (3)
O4—O5—H5	109.00	C20—C21—C22	122.9 (3)
C5—N1—C6	127.44 (17)	C21—C22—C23	118.3 (3)
C5—N1—H1	116.4 (14)	C18—C23—C22	120.9 (2)
C6—N1—H1	116.1 (14)	C4—C24—C26	113.12 (18)
O1—C1—C2	104.45 (14)	C25—C24—C26	111.13 (19)
O1—C1—C18	107.99 (15)	C4—C24—C25	112.29 (18)
O1—C1—O2	111.48 (15)	C6—C7—H7	120.00
O2—C1—C2	110.37 (15)	C8—C7—H7	120.00
O2—C1—C18	108.49 (15)	C7—C8—H8	120.00
C2—C1—C18	114.03 (15)	C9—C8—H8	120.00
O3—C2—C3	58.97 (11)	C8—C9—H9	120.00
O3—C2—C12	118.22 (15)	C10—C9—H9	120.00
C1—C2—C3	106.41 (15)	C9—C10—H10	119.00
O3—C2—C1	109.96 (14)	C11—C10—H10	119.00
C1—C2—C12	121.45 (16)	C6—C11—H11	120.00
C3—C2—C12	125.76 (17)	C10—C11—H11	120.00
O3—C3—C5	118.09 (15)	C12—C13—H13	120.00
C4—C3—C5	121.71 (16)	C14—C13—H13	120.00
C2—C3—C4	108.17 (15)	C13—C14—H14	120.00
C2—C3—C5	123.01 (16)	C15—C14—H14	120.00
O3—C3—C2	59.83 (11)	C14—C15—H15	120.00
O3—C3—C4	110.33 (15)	C16—C15—H15	120.00
O4—C4—C24	105.89 (16)	C15—C16—H16	120.00
C3—C4—C24	115.00 (16)	C17—C16—H16	120.00
O1—C4—C24	108.21 (16)	C12—C17—H17	120.00
O1—C4—O4	110.64 (15)	C16—C17—H17	120.00
O1—C4—C3	104.07 (15)	C18—C19—H19	120.00
O4—C4—C3	112.99 (15)	C20—C19—H19	120.00
O6—C5—N1	124.85 (18)	C19—C20—H20	121.00
N1—C5—C3	116.01 (16)	C21—C20—H20	121.00
O6—C5—C3	119.15 (17)	C21—C22—H22	121.00
N1—C6—C11	122.63 (19)	C23—C22—H22	121.00
C7—C6—C11	119.54 (19)	C18—C23—H23	120.00
N1—C6—C7	117.81 (18)	C22—C23—H23	120.00
C6—C7—C8	120.1 (2)	C4—C24—H24	104.8 (14)
C7—C8—C9	120.2 (3)	C25—C24—H24	108.0 (14)
C8—C9—C10	119.8 (3)	C26—C24—H24	107.0 (13)
C9—C10—C11	121.2 (3)	C24—C25—H25A	109.00
C6—C11—C10	119.2 (2)	C24—C25—H25B	109.00
C2—C12—C13	120.23 (18)	C24—C25—H25C	109.00
C2—C12—C17	120.97 (18)	H25A—C25—H25B	110.00
C13—C12—C17	118.8 (2)	H25A—C25—H25C	109.00
C12—C13—C14	120.9 (2)	H25B—C25—H25C	109.00
C13—C14—C15	119.4 (2)	C24—C26—H26A	109.00
C14—C15—C16	120.7 (2)	C24—C26—H26B	109.00
C15—C16—C17	120.4 (3)	C24—C26—H26C	109.00
C12—C17—C16	119.8 (2)	H26A—C26—H26B	109.00
C19—C18—C23	118.79 (19)	H26A—C26—H26C	109.00
C1—C18—C19	120.47 (18)	H26B—C26—H26C	109.00
C1—C18—C23	120.69 (18)

C4—O1—C1—O2	100.71 (17)	O3—C3—C4—O4	173.71 (14)
C4—O1—C1—C2	−18.48 (18)	O3—C3—C4—C24	−64.6 (2)
C4—O1—C1—C18	−140.20 (15)	C2—C3—C4—O1	−10.10 (19)
C1—O1—C4—O4	−103.48 (17)	C2—C3—C4—O4	109.97 (17)
C1—O1—C4—C3	18.17 (19)	C2—C3—C4—C24	−128.29 (17)
C1—O1—C4—C24	140.93 (16)	C5—C3—C4—O1	−161.36 (16)
C3—O3—C2—C1	97.59 (16)	C5—C3—C4—O4	−41.3 (2)
C3—O3—C2—C12	−116.82 (19)	C5—C3—C4—C24	80.5 (2)
C2—O3—C3—C4	−99.75 (16)	O3—C3—C5—O6	−166.15 (17)
C2—O3—C3—C5	113.84 (19)	O3—C3—C5—N1	13.7 (3)
O5—O4—C4—O1	68.46 (18)	C2—C3—C5—O6	−95.6 (2)
O5—O4—C4—C3	−47.78 (19)	C2—C3—C5—N1	84.3 (2)
O5—O4—C4—C24	−174.52 (14)	C4—C3—C5—O6	51.4 (3)
C6—N1—C5—O6	0.3 (3)	C4—C3—C5—N1	−128.75 (19)
C6—N1—C5—C3	−179.54 (18)	O1—C4—C24—C25	58.3 (2)
C5—N1—C6—C7	−161.4 (2)	O1—C4—C24—C26	−174.90 (17)
C5—N1—C6—C11	20.3 (3)	O4—C4—C24—C25	−60.3 (2)
O1—C1—C2—O3	−51.65 (17)	O4—C4—C24—C26	66.5 (2)
O1—C1—C2—C3	10.65 (18)	C3—C4—C24—C25	174.17 (18)
O1—C1—C2—C12	164.07 (15)	C3—C4—C24—C26	−59.1 (2)
O2—C1—C2—O3	−171.59 (14)	N1—C6—C7—C8	−178.3 (2)
O2—C1—C2—C3	−109.29 (16)	C11—C6—C7—C8	0.1 (3)
O2—C1—C2—C12	44.1 (2)	N1—C6—C11—C10	177.7 (2)
C18—C1—C2—O3	66.0 (2)	C7—C6—C11—C10	−0.6 (4)
C18—C1—C2—C3	128.30 (16)	C6—C7—C8—C9	0.4 (4)
C18—C1—C2—C12	−78.3 (2)	C7—C8—C9—C10	−0.4 (4)
O1—C1—C18—C19	−160.88 (18)	C8—C9—C10—C11	−0.1 (4)
O1—C1—C18—C23	21.9 (2)	C9—C10—C11—C6	0.6 (4)
O2—C1—C18—C19	−39.9 (2)	C2—C12—C13—C14	177.9 (2)
O2—C1—C18—C23	142.86 (19)	C17—C12—C13—C14	−0.5 (3)
C2—C1—C18—C19	83.5 (2)	C2—C12—C17—C16	−176.6 (2)
C2—C1—C18—C23	−93.7 (2)	C13—C12—C17—C16	1.7 (4)
O3—C2—C3—C4	103.43 (15)	C12—C13—C14—C15	−1.2 (4)
O3—C2—C3—C5	−105.77 (18)	C13—C14—C15—C16	1.7 (4)
C1—C2—C3—O3	−103.78 (15)	C14—C15—C16—C17	−0.4 (5)
C1—C2—C3—C4	−0.35 (19)	C15—C16—C17—C12	−1.3 (4)
C1—C2—C3—C5	150.45 (16)	C1—C18—C19—C20	−178.2 (2)
C12—C2—C3—O3	104.29 (19)	C23—C18—C19—C20	−0.9 (3)
C12—C2—C3—C4	−152.28 (17)	C1—C18—C23—C22	179.0 (2)
C12—C2—C3—C5	−1.5 (3)	C19—C18—C23—C22	1.7 (3)
O3—C2—C12—C13	121.7 (2)	C18—C19—C20—C21	−1.0 (4)
O3—C2—C12—C17	−60.0 (3)	C19—C20—C21—F1	−177.8 (3)
C1—C2—C12—C13	−96.8 (2)	C19—C20—C21—C22	2.2 (5)
C1—C2—C12—C17	81.5 (2)	F1—C21—C22—C23	178.6 (3)
C3—C2—C12—C13	51.3 (3)	C20—C21—C22—C23	−1.4 (5)
C3—C2—C12—C17	−130.4 (2)	C21—C22—C23—C18	−0.6 (4)
O3—C3—C4—O1	53.64 (18)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O3	0.86 (2)	2.36 (2)	2.780 (2)	110.8 (17)
N1—H1···O2ⁱ	0.86 (2)	2.37 (2)	3.216 (2)	168.0 (18)
O2—H2···O5	0.84 (2)	2.15 (2)	2.920 (2)	152 (2)
O2—H2···O3ⁱⁱ	0.84 (2)	2.35 (2)	2.8188 (18)	116.1 (18)
O5—H5···O6	0.8200	1.9900	2.655 (2)	138.00

Symmetry codes: (i) −x+3/2, y−1/2, −z+1/2; (ii) −x+3/2, y+1/2, −z+1/2.

Experimental details

Crystal data
Chemical formula	C₂₆H₂₄FNO₆
M_r	465.46
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	296
a, b, c (Å)	11.7560 (6), 11.7489 (6), 17.0889 (9)
β (°)	94.438 (2)
V (Å³)	2353.2 (2)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.25 × 0.18 × 0.15

Data collection
Diffractometer	Bruker Kappa APEXII CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2005)
T_min, T_max	0.975, 0.980
No. of measured, independent and observed [I > 2σ(I)] reflections	14754, 5340, 3008
R_int	0.040
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.136, 1.02
No. of reflections	5340
No. of parameters	318
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.34, −0.28

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997) and PLATON (Spek, 2003), WinGX (Farrugia, 1999) and PLATON (Spek, 2003).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O3	0.86 (2)	2.36 (2)	2.780 (2)	110.8 (17)
N1—H1···O2ⁱ	0.86 (2)	2.37 (2)	3.216 (2)	168.0 (18)
O2—H2···O5	0.84 (2)	2.15 (2)	2.920 (2)	152 (2)
O2—H2···O3ⁱⁱ	0.84 (2)	2.35 (2)	2.8188 (18)	116.1 (18)
O5—H5···O6	0.8200	1.9900	2.655 (2)	138.00

Symmetry codes: (i) −x+3/2, y−1/2, −z+1/2; (ii) −x+3/2, y+1/2, −z+1/2.

Acknowledgements

MA gratefully acknowledges the Higher Education Commision, Islamabad, Pakistan, for providing him with a scholaship under the Indigenous PhD Program (PIN 042-120556-PS2-275).

References

Bruker (2005). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358. CrossRef CAS Web of Science 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
United States Pharmacopeia (2007). United States Pharmacopoeia, 2nd ed. Rockville: United States Pharmacopial Convention. Google Scholar
Rouleau, J. (2005). Am. J. Med. 118 (Suppl. 12A), 28–35. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13. Web of Science CrossRef CAS IUCr Journals Google Scholar

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Volume 64| Part 8| August 2008| Page o1548

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Degradation of atorvastatin: (1R,2S,4S,5S)-4-(4-fluoro­phen­yl)-2-hydro­per­oxy-4-hydr­­oxy-2-iso­propyl-N,5-di­phenyl-3,6-dioxabi­cyclo­[3.1.0]hexane-1-carboxamide

Related literature

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

Degradation of atorvastatin: (1R,2S,4S,5S)-4-(4-fluorophenyl)-2-hydroperoxy-4-hydroxy-2-isopropyl-N,5-diphenyl-3,6-dioxabicyclo[3.1.0]hexane-1-carboxamide