Benzyl 2-benzyl-4-[(3aS,7aR)-2,3,3a,4,5,6,7,7a-octa­hydro-1H-isoindol-2-yl]-4-oxobutano­ate

Shang, Z.; Xu, L.; Zheng, L.; Zhang, Y.

doi:10.1107/S1600536812037567

organic compounds

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ISSN: 2056-9890

Volume 68| Part 10| October 2012| Page o2853

https://doi.org/10.1107/S1600536812037567

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Benzyl 2-benzyl-4-[(3aS,7aR)-2,3,3a,4,5,6,7,7a-octahydro-1H-isoindol-2-yl]-4-oxobutanoate

Zhenhua Shang,^a ^* Longpeng Xu,^b Ligang Zheng ^c and Yong Zhang ^b

^aCollege of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Hebei Research Center of Pharmaceutical and Chemical Engineering, State Key Laboratory Breeding Base–Hebei Province Key Laboratory of Molecular Chemistry for Drugs, Shijiazhuang 050018, People's Republic of China, ^bCollege of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, People's Republic of China, and ^cZhongqi Pharmacy (Shijiazhang), Shijiazhuang Pharmaceutical Group Co., Ltd (CSPC) , Shijiazhuang 050051, People's Republic of China
^*Correspondence e-mail: zhenhuashang@yahoo.com.cn

(Received 22 August 2012; accepted 31 August 2012; online 5 September 2012)

In the title compound, C₂₆H₃₁NO₃, the octahydro-1H-isoindole ring is not planar and the two rings are twisted with a C—C—C—C torsion angle of 73.6 (4)°. The six-membered ring has a chair conformation while the five-membered ring has an envelope conformation on the C-atom in position 7a. The H atoms in the 3a- and 7a-psitions are cis and the H—C—C—H torsion angle is 42.36°.

Related literature

The title compound is an intermediate of mitiglinide, which was obtained when 2-benzyl-4-[(3aS,7aR)-2,3,3a,4,5,6,7,7a-octahydro-1H-isoindol-2-yl]-4-oxobutanoic acid was reacted with 1-(chloromethyl)benzene in ethyl acetate with potassium iodide as catalyst. For the use of mitiglinide, a potassium channel antagonist, in the treatment of type 2 diabetes, see: Reimann et al. (2001 ).

Experimental

Crystal data

C₂₆H₃₁NO₃
M_r = 405.52
Triclinic, P 1
a = 5.8542 (12) Å
b = 9.0365 (18) Å
c = 11.352 (2) Å
α = 108.59 (3)°
β = 93.94 (3)°
γ = 101.23 (3)°
V = 552.7 (2) Å³
Z = 1
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 294 K
0.16 × 0.14 × 0.10 mm

Data collection

Rigaku Saturn70 CCD diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005 ) T_min = 0.988, T_max = 0.992
5536 measured reflections
2588 independent reflections
1424 reflections with I > 2σ(I)
R_int = 0.049

Refinement

R[F² > 2σ(F²)] = 0.043
wR(F²) = 0.106
S = 0.89
2588 reflections
271 parameters
3 restraints
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: CrystalClear (Rigaku, 2005); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536812037567/hg5245sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812037567/hg5245Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536812037567/hg5245Isup3.cml

checkCIF report

Comment top

Mitiglinide, a potassium channel antagonist produced by Kissei Pharmaceutical Co., Ltd, was used for the treatment of type 2 diabetes mellitus (Reimann et al., 2001). The title compound, as the key intermediate, was obtained When 2-benzyl-4-((3aS,7aR)-hexahydro -1H-isoindol-2(3H)-yl)-4-oxobutanoic acid was reacted with 1-(chloromethyl)benzene in ethyl acetate with potassium iodide as the catalyst. The octahydro-1H-isoindole ring is not on a plane and the two rings are twisted (C5—C6—C7—C8 = 73.6 (4)°, C3—C2—C1 = 112.5 (3)°, C4—C5—C6 = 111.2 (3)°). The 8-aza bicyclo[4.3.0]nonane ring is almost chair conformation (N1—C1—C2 = 102.8 (2)°, N1—C8—C7 = 105.1 (2)°), The C2 and C7 H atoms are cis form with the H2—C2—C7—H7 torsion angle 42.36°.

Related literature top

The title compound is the key intermediate of mitiglinide, which was obtained when 2-benzyl-4-[(3aS,7aR)-2,3,3a,4,5,6,7,7a-octahydro-1H-isoindol-2-yl]-4-oxobutanoic acid was reacted with 1-(chloromethyl)benzene in ethyl acetate with potassium iodide as the catalyst. For the use of mitiglinide, a potassium channel antagonist, in the treatment of type 2 diabetes, see: Reimann et al. (2001).

Experimental top

To a solution of 2-benzyl-4-((3aS,7aR)-hexahydro-1H-isoindol-2(3H)-yl) -4-oxobutanoic acid (13.8 g), KI (0.8 g) and potassium carbonate (6.6 g) in ethyl acetate (50 ml), 1-(chloromethyl)benzene (3.7 g) was added droply. After addition, the mixture was heated and reflux for 21 h. The reaction mixture was poured into 60 ml ice-water. The organic layer was seperated and distilled. When the ethyl acetate was recovered, the residue was added 120 ml petroleum ether. The product was obtained through filtration and recystalled. 50 mg of the title compound was dissolved in 50 ml ethanol and the solution was kept at room temperature for 10 d for natural evaporation. Colorless single crystals of the title compound obtained was suitable for X-ray analysis.

Structure description top

Computing details top

Data collection: CrystalClear (Rigaku, 2005); cell refinement: CrystalClear (Rigaku, 2005); data reduction: CrystalClear (Rigaku, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

Fig. 1. The molecular structure of the title compound, drawn with 30% probability ellipsoids.

Benzyl 2-benzyl-4-[(3aS,7aR)-2,3,3a,4,5,6,7,7a- octahydro-1H-isoindol-2-yl]-4-oxobutanoate top

Crystal data top

C₂₆H₃₁NO₃	Z = 1
M_r = 405.52	F(000) = 218
Triclinic, P1	D_x = 1.218 Mg m⁻³
Hall symbol: P 1	Mo Kα radiation, λ = 0.71073 Å
a = 5.8542 (12) Å	Cell parameters from 1681 reflections
b = 9.0365 (18) Å	θ = 1.9–27.9°
c = 11.352 (2) Å	µ = 0.08 mm⁻¹
α = 108.59 (3)°	T = 294 K
β = 93.94 (3)°	Plate, colorless
γ = 101.23 (3)°	0.16 × 0.14 × 0.10 mm
V = 552.7 (2) Å³

Data collection top

Rigaku Saturn70 CCD diffractometer	2588 independent reflections
Radiation source: rotating anode	1424 reflections with I > 2σ(I)
Multilayer monochromator	R_int = 0.049
Detector resolution: 7.31 pixels mm^-1	θ_max = 27.9°, θ_min = 1.9°
ω scans	h = −7→7
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005)	k = −11→10
T_min = 0.988, T_max = 0.992	l = −14→14
5536 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.106	H-atom parameters constrained
S = 0.89	w = 1/[σ²(F_o²) + (0.0499P)²] where P = (F_o² + 2F_c²)/3
2588 reflections	(Δ/σ)_max = 0.002
271 parameters	Δρ_max = 0.18 e Å⁻³
3 restraints	Δρ_min = −0.20 e Å⁻³

Crystal data top

C₂₆H₃₁NO₃	γ = 101.23 (3)°
M_r = 405.52	V = 552.7 (2) Å³
Triclinic, P1	Z = 1
a = 5.8542 (12) Å	Mo Kα radiation
b = 9.0365 (18) Å	µ = 0.08 mm⁻¹
c = 11.352 (2) Å	T = 294 K
α = 108.59 (3)°	0.16 × 0.14 × 0.10 mm
β = 93.94 (3)°

Data collection top

Rigaku Saturn70 CCD diffractometer	2588 independent reflections
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005)	1424 reflections with I > 2σ(I)
T_min = 0.988, T_max = 0.992	R_int = 0.049
5536 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	3 restraints
wR(F²) = 0.106	H-atom parameters constrained
S = 0.89	Δρ_max = 0.18 e Å⁻³
2588 reflections	Δρ_min = −0.20 e Å⁻³
271 parameters

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
O1	−0.1006 (3)	0.2391 (3)	0.4493 (2)	0.0461 (6)
O2	0.2379 (5)	0.2088 (3)	0.7354 (3)	0.0781 (9)
O3	0.0275 (4)	0.3929 (3)	0.7968 (2)	0.0530 (6)
N1	0.1082 (4)	0.0726 (3)	0.3389 (2)	0.0414 (7)
C1	0.3247 (5)	0.0184 (4)	0.3070 (3)	0.0460 (8)
H1A	0.3538	−0.0562	0.3485	0.055*
H1B	0.4599	0.1083	0.3300	0.055*
C2	0.2709 (5)	−0.0637 (4)	0.1651 (3)	0.0388 (7)
H2	0.3633	−0.1449	0.1378	0.047*
C3	0.3173 (6)	0.0541 (4)	0.0949 (3)	0.0500 (9)
H3A	0.2529	0.1458	0.1348	0.060*
H3B	0.4858	0.0921	0.1003	0.060*
C4	0.2112 (7)	−0.0190 (5)	−0.0407 (4)	0.0660 (11)
H4A	0.2796	−0.1082	−0.0821	0.079*
H4B	0.2458	0.0602	−0.0819	0.079*
C5	−0.0515 (7)	−0.0771 (5)	−0.0518 (4)	0.0683 (12)
H5A	−0.1179	−0.1232	−0.1398	0.082*
H5B	−0.1199	0.0131	−0.0131	0.082*
C6	−0.1126 (6)	−0.2014 (4)	0.0109 (3)	0.0551 (10)
H6A	−0.0674	−0.2984	−0.0369	0.066*
H6B	−0.2816	−0.2274	0.0102	0.066*
C7	0.0077 (5)	−0.1453 (4)	0.1451 (3)	0.0422 (8)
H7	−0.0069	−0.2393	0.1719	0.051*
C8	−0.0910 (5)	−0.0199 (4)	0.2404 (3)	0.0452 (8)
H8A	−0.1499	0.0490	0.2014	0.054*
H8B	−0.2179	−0.0713	0.2748	0.054*
C9	0.0902 (5)	0.2018 (4)	0.4337 (3)	0.0352 (7)
C10	0.3132 (5)	0.3000 (4)	0.5201 (3)	0.0392 (7)
H10A	0.4084	0.3610	0.4772	0.047*
H10B	0.4018	0.2282	0.5389	0.047*
C11	0.2690 (5)	0.4157 (4)	0.6433 (3)	0.0383 (7)
H11	0.1502	0.4708	0.6243	0.046*
C12	0.4942 (6)	0.5424 (4)	0.7134 (3)	0.0505 (9)
H12A	0.4676	0.5993	0.7976	0.061*
H12B	0.6203	0.4888	0.7205	0.061*
C13	0.5688 (5)	0.6615 (4)	0.6478 (3)	0.0400 (7)
C14	0.4546 (6)	0.7839 (4)	0.6598 (3)	0.0517 (9)
H14	0.3265	0.7878	0.7040	0.062*
C15	0.5261 (7)	0.9007 (4)	0.6076 (3)	0.0639 (11)
H15	0.4469	0.9826	0.6171	0.077*
C16	0.7108 (7)	0.8964 (5)	0.5428 (4)	0.0687 (11)
H16	0.7600	0.9756	0.5082	0.082*
C17	0.8251 (7)	0.7751 (6)	0.5284 (4)	0.0755 (13)
H17	0.9516	0.7715	0.4831	0.091*
C18	0.7548 (6)	0.6577 (5)	0.5804 (4)	0.0589 (10)
H18	0.8339	0.5756	0.5697	0.071*
C19	0.1781 (6)	0.3255 (4)	0.7267 (3)	0.0439 (8)
C20	−0.0779 (7)	0.3150 (5)	0.8789 (3)	0.0586 (10)
H20A	−0.0677	0.2035	0.8495	0.070*
H20B	−0.2432	0.3172	0.8749	0.070*
C21	0.0366 (6)	0.3918 (4)	1.0121 (3)	0.0465 (8)
C22	0.2699 (6)	0.4696 (5)	1.0456 (4)	0.0586 (10)
H22	0.3625	0.4787	0.9838	0.070*
C23	0.3670 (8)	0.5339 (5)	1.1696 (4)	0.0681 (11)
H23	0.5252	0.5862	1.1909	0.082*
C24	0.2340 (9)	0.5220 (5)	1.2627 (4)	0.0724 (12)
H24	0.3005	0.5667	1.3467	0.087*
C25	0.0015 (9)	0.4432 (5)	1.2297 (4)	0.0730 (13)
H25	−0.0898	0.4315	1.2915	0.088*
C26	−0.0973 (7)	0.3812 (4)	1.1053 (4)	0.0564 (9)
H26	−0.2565	0.3316	1.0840	0.068*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0369 (12)	0.0497 (13)	0.0454 (14)	0.0100 (10)	0.0056 (10)	0.0075 (11)
O2	0.122 (2)	0.0620 (17)	0.083 (2)	0.0488 (17)	0.0506 (18)	0.0457 (16)
O3	0.0657 (15)	0.0563 (15)	0.0471 (15)	0.0236 (12)	0.0191 (12)	0.0233 (12)
N1	0.0273 (13)	0.0517 (16)	0.0349 (15)	0.0075 (12)	−0.0012 (11)	0.0028 (13)
C1	0.0328 (17)	0.056 (2)	0.044 (2)	0.0137 (14)	0.0036 (15)	0.0085 (16)
C2	0.0368 (16)	0.0396 (18)	0.0369 (18)	0.0121 (13)	0.0034 (13)	0.0070 (14)
C3	0.0440 (18)	0.055 (2)	0.055 (2)	0.0111 (16)	0.0147 (16)	0.0213 (18)
C4	0.088 (3)	0.079 (3)	0.042 (2)	0.028 (2)	0.017 (2)	0.028 (2)
C5	0.084 (3)	0.079 (3)	0.035 (2)	0.025 (2)	−0.0119 (19)	0.010 (2)
C6	0.057 (2)	0.048 (2)	0.042 (2)	0.0109 (17)	−0.0080 (17)	−0.0052 (17)
C7	0.0438 (18)	0.0321 (17)	0.042 (2)	0.0040 (14)	0.0001 (15)	0.0054 (15)
C8	0.0309 (16)	0.052 (2)	0.0377 (19)	0.0009 (14)	−0.0017 (14)	0.0019 (15)
C9	0.0310 (15)	0.0403 (17)	0.0323 (17)	0.0027 (13)	0.0034 (12)	0.0130 (14)
C10	0.0348 (16)	0.0454 (18)	0.0341 (18)	0.0055 (13)	0.0028 (13)	0.0116 (15)
C11	0.0441 (17)	0.0372 (17)	0.0297 (17)	0.0082 (14)	−0.0007 (14)	0.0082 (14)
C12	0.062 (2)	0.0398 (19)	0.042 (2)	0.0000 (16)	−0.0092 (16)	0.0134 (16)
C13	0.0426 (18)	0.0352 (17)	0.0335 (17)	0.0024 (13)	−0.0067 (14)	0.0063 (13)
C14	0.067 (2)	0.046 (2)	0.042 (2)	0.0200 (18)	0.0127 (17)	0.0092 (16)
C15	0.087 (3)	0.041 (2)	0.062 (3)	0.018 (2)	0.007 (2)	0.015 (2)
C16	0.079 (3)	0.055 (2)	0.068 (3)	−0.003 (2)	0.002 (2)	0.028 (2)
C17	0.048 (2)	0.097 (4)	0.082 (3)	0.005 (2)	0.017 (2)	0.038 (3)
C18	0.049 (2)	0.059 (2)	0.070 (3)	0.0163 (18)	0.0054 (19)	0.022 (2)
C19	0.0541 (19)	0.0417 (19)	0.0372 (19)	0.0149 (16)	0.0051 (15)	0.0132 (15)
C20	0.059 (2)	0.072 (3)	0.052 (2)	0.0118 (19)	0.0156 (19)	0.030 (2)
C21	0.058 (2)	0.044 (2)	0.047 (2)	0.0195 (17)	0.0160 (17)	0.0224 (17)
C22	0.061 (2)	0.065 (2)	0.053 (2)	0.018 (2)	0.0123 (19)	0.021 (2)
C23	0.074 (3)	0.062 (3)	0.067 (3)	0.017 (2)	0.005 (2)	0.021 (2)
C24	0.114 (4)	0.057 (3)	0.047 (3)	0.030 (3)	0.000 (3)	0.015 (2)
C25	0.115 (4)	0.059 (3)	0.057 (3)	0.026 (3)	0.038 (3)	0.028 (2)
C26	0.069 (2)	0.053 (2)	0.055 (2)	0.0170 (18)	0.023 (2)	0.0240 (19)

Geometric parameters (Å, º) top

O1—C9	1.236 (3)	C10—H10B	0.9700
O2—C19	1.204 (4)	C11—C19	1.495 (5)
O3—C19	1.334 (4)	C11—C12	1.539 (4)
O3—C20	1.440 (4)	C11—H11	0.9800
N1—C9	1.340 (4)	C12—C13	1.509 (5)
N1—C8	1.468 (4)	C12—H12A	0.9700
N1—C1	1.473 (4)	C12—H12B	0.9700
C1—C2	1.524 (4)	C13—C18	1.373 (5)
C1—H1A	0.9700	C13—C14	1.376 (4)
C1—H1B	0.9700	C14—C15	1.379 (5)
C2—C3	1.516 (4)	C14—H14	0.9300
C2—C7	1.541 (4)	C15—C16	1.348 (5)
C2—H2	0.9800	C15—H15	0.9300
C3—C4	1.501 (5)	C16—C17	1.364 (6)
C3—H3A	0.9700	C16—H16	0.9300
C3—H3B	0.9700	C17—C18	1.381 (6)
C4—C5	1.507 (6)	C17—H17	0.9300
C4—H4A	0.9700	C18—H18	0.9300
C4—H4B	0.9700	C20—C21	1.493 (5)
C5—C6	1.512 (5)	C20—H20A	0.9700
C5—H5A	0.9700	C20—H20B	0.9700
C5—H5B	0.9700	C21—C22	1.374 (5)
C6—C7	1.515 (5)	C21—C26	1.375 (4)
C6—H6A	0.9700	C22—C23	1.372 (5)
C6—H6B	0.9700	C22—H22	0.9300
C7—C8	1.532 (4)	C23—C24	1.374 (6)
C7—H7	0.9800	C23—H23	0.9300
C8—H8A	0.9700	C24—C25	1.372 (7)
C8—H8B	0.9700	C24—H24	0.9300
C9—C10	1.507 (4)	C25—C26	1.379 (6)
C10—C11	1.529 (4)	C25—H25	0.9300
C10—H10A	0.9700	C26—H26	0.9300

C19—O3—C20	117.8 (3)	C11—C10—H10B	108.9
C9—N1—C8	121.5 (2)	H10A—C10—H10B	107.7
C9—N1—C1	127.0 (2)	C19—C11—C10	110.2 (3)
C8—N1—C1	110.9 (2)	C19—C11—C12	109.0 (3)
N1—C1—C2	102.8 (2)	C10—C11—C12	111.7 (3)
N1—C1—H1A	111.2	C19—C11—H11	108.6
C2—C1—H1A	111.2	C10—C11—H11	108.6
N1—C1—H1B	111.2	C12—C11—H11	108.6
C2—C1—H1B	111.2	C13—C12—C11	112.4 (3)
H1A—C1—H1B	109.1	C13—C12—H12A	109.1
C3—C2—C1	112.5 (3)	C11—C12—H12A	109.1
C3—C2—C7	111.5 (3)	C13—C12—H12B	109.1
C1—C2—C7	102.8 (3)	C11—C12—H12B	109.1
C3—C2—H2	109.9	H12A—C12—H12B	107.9
C1—C2—H2	109.9	C18—C13—C14	117.9 (3)
C7—C2—H2	109.9	C18—C13—C12	122.6 (3)
C4—C3—C2	112.4 (3)	C14—C13—C12	119.5 (3)
C4—C3—H3A	109.1	C13—C14—C15	121.3 (3)
C2—C3—H3A	109.1	C13—C14—H14	119.3
C4—C3—H3B	109.1	C15—C14—H14	119.3
C2—C3—H3B	109.1	C16—C15—C14	120.1 (3)
H3A—C3—H3B	107.8	C16—C15—H15	119.9
C3—C4—C5	110.2 (3)	C14—C15—H15	119.9
C3—C4—H4A	109.6	C15—C16—C17	119.7 (4)
C5—C4—H4A	109.6	C15—C16—H16	120.2
C3—C4—H4B	109.6	C17—C16—H16	120.2
C5—C4—H4B	109.6	C16—C17—C18	120.6 (4)
H4A—C4—H4B	108.1	C16—C17—H17	119.7
C4—C5—C6	111.2 (3)	C18—C17—H17	119.7
C4—C5—H5A	109.4	C13—C18—C17	120.4 (3)
C6—C5—H5A	109.4	C13—C18—H18	119.8
C4—C5—H5B	109.4	C17—C18—H18	119.8
C6—C5—H5B	109.4	O2—C19—O3	122.4 (3)
H5A—C5—H5B	108.0	O2—C19—C11	125.2 (3)
C5—C6—C7	112.8 (3)	O3—C19—C11	112.3 (3)
C5—C6—H6A	109.0	O3—C20—C21	112.9 (3)
C7—C6—H6A	109.0	O3—C20—H20A	109.0
C5—C6—H6B	109.0	C21—C20—H20A	109.0
C7—C6—H6B	109.0	O3—C20—H20B	109.0
H6A—C6—H6B	107.8	C21—C20—H20B	109.0
C6—C7—C8	115.5 (3)	H20A—C20—H20B	107.8
C6—C7—C2	114.9 (3)	C22—C21—C26	118.7 (3)
C8—C7—C2	102.4 (2)	C22—C21—C20	123.1 (3)
C6—C7—H7	107.8	C26—C21—C20	118.2 (3)
C8—C7—H7	107.8	C23—C22—C21	120.5 (4)
C2—C7—H7	107.8	C23—C22—H22	119.8
N1—C8—C7	105.1 (2)	C21—C22—H22	119.8
N1—C8—H8A	110.7	C22—C23—C24	120.9 (4)
C7—C8—H8A	110.7	C22—C23—H23	119.5
N1—C8—H8B	110.7	C24—C23—H23	119.5
C7—C8—H8B	110.7	C25—C24—C23	118.9 (4)
H8A—C8—H8B	108.8	C25—C24—H24	120.6
O1—C9—N1	121.5 (3)	C23—C24—H24	120.6
O1—C9—C10	121.5 (3)	C24—C25—C26	120.2 (4)
N1—C9—C10	117.0 (2)	C24—C25—H25	119.9
C9—C10—C11	113.3 (2)	C26—C25—H25	119.9
C9—C10—H10A	108.9	C21—C26—C25	120.8 (4)
C11—C10—H10A	108.9	C21—C26—H26	119.6
C9—C10—H10B	108.9	C25—C26—H26	119.6

C9—N1—C1—C2	−149.7 (3)	C10—C11—C12—C13	70.1 (3)
C8—N1—C1—C2	21.3 (3)	C11—C12—C13—C18	−104.7 (4)
N1—C1—C2—C3	83.2 (3)	C11—C12—C13—C14	78.3 (4)
N1—C1—C2—C7	−36.9 (3)	C18—C13—C14—C15	−1.0 (5)
C1—C2—C3—C4	−166.1 (3)	C12—C13—C14—C15	176.1 (3)
C7—C2—C3—C4	−51.2 (4)	C13—C14—C15—C16	0.3 (5)
C2—C3—C4—C5	59.6 (4)	C14—C15—C16—C17	0.5 (6)
C3—C4—C5—C6	−59.5 (4)	C15—C16—C17—C18	−0.6 (6)
C4—C5—C6—C7	52.5 (4)	C14—C13—C18—C17	0.9 (5)
C5—C6—C7—C8	73.6 (4)	C12—C13—C18—C17	−176.1 (4)
C5—C6—C7—C2	−45.4 (4)	C16—C17—C18—C13	−0.2 (6)
C3—C2—C7—C6	44.2 (4)	C20—O3—C19—O2	−4.4 (5)
C1—C2—C7—C6	165.0 (3)	C20—O3—C19—C11	178.4 (3)
C3—C2—C7—C8	−81.8 (3)	C10—C11—C19—O2	36.0 (4)
C1—C2—C7—C8	38.9 (3)	C12—C11—C19—O2	−86.9 (4)
C9—N1—C8—C7	174.7 (3)	C10—C11—C19—O3	−146.9 (3)
C1—N1—C8—C7	3.2 (3)	C12—C11—C19—O3	90.2 (3)
C6—C7—C8—N1	−151.8 (3)	C19—O3—C20—C21	100.6 (4)
C2—C7—C8—N1	−26.1 (3)	O3—C20—C21—C22	−29.7 (5)
C8—N1—C9—O1	7.4 (4)	O3—C20—C21—C26	151.6 (3)
C1—N1—C9—O1	177.6 (3)	C26—C21—C22—C23	0.6 (5)
C8—N1—C9—C10	−172.3 (3)	C20—C21—C22—C23	−178.1 (3)
C1—N1—C9—C10	−2.2 (4)	C21—C22—C23—C24	0.0 (6)
O1—C9—C10—C11	15.8 (4)	C22—C23—C24—C25	0.6 (6)
N1—C9—C10—C11	−164.5 (3)	C23—C24—C25—C26	−1.8 (6)
C9—C10—C11—C19	73.2 (3)	C22—C21—C26—C25	−1.9 (5)
C9—C10—C11—C12	−165.5 (2)	C20—C21—C26—C25	176.9 (4)
C19—C11—C12—C13	−167.8 (3)	C24—C25—C26—C21	2.5 (6)

Experimental details

Crystal data
Chemical formula	C₂₆H₃₁NO₃
M_r	405.52
Crystal system, space group	Triclinic, P1
Temperature (K)	294
a, b, c (Å)	5.8542 (12), 9.0365 (18), 11.352 (2)
α, β, γ (°)	108.59 (3), 93.94 (3), 101.23 (3)
V (Å³)	552.7 (2)
Z	1
Radiation type	Mo Kα
µ (mm⁻¹)	0.08
Crystal size (mm)	0.16 × 0.14 × 0.10

Data collection
Diffractometer	Rigaku Saturn70 CCD
Absorption correction	Multi-scan (CrystalClear; Rigaku, 2005)
T_min, T_max	0.988, 0.992
No. of measured, independent and observed [I > 2σ(I)] reflections	5536, 2588, 1424
R_int	0.049
(sin θ/λ)_max (Å⁻¹)	0.658

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.106, 0.89
No. of reflections	2588
No. of parameters	271
No. of restraints	3
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.20

Computer programs: CrystalClear (Rigaku, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Acknowledgements

This work was supported by the Natural Science Foundation of Hebei Province (H2012208045), the Scientific and Technological Major Special Project (Major Creation of New Drugs, No. 2011ZX09202–101-22) and the Program for Innovative Research Team of Hebei University of Science and Technology. The authors thank Dr Haibin Song of Nankai University for the data collection and stucture determination.

References

Reimann, F., Prokes, P. & Ashcroft, F. M. (2001). Br. J. Pharmacol. 132, 1542–1548. Web of Science CrossRef PubMed CAS Google Scholar
Rigaku (2005). CrystalClear. Rigaku Corporation, Tokyo, Japan. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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