organic compounds
Benzyl 2-benzyl-4-[(3aS,7aR)-2,3,3a,4,5,6,7,7a-octahydro-1H-isoindol-2-yl]-4-oxobutanoate
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
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 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
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Data collection: CrystalClear (Rigaku, 2005); cell 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
https://doi.org/10.1107/S1600536812037567/hg5245sup1.cif
contains datablocks global, I. DOI: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
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.
All H atoms attached to C atoms were fixed geometrically and treated as riding with C—H = 0.93 Å (aromatic), 0.98 Å (tertiary methyl CH group) or 0.97 Å (secondary CH2 group), with Uiso(H)=1.2Ueq(C). The merging of the Friedel pairs are 3840–2588 = 1252.
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°.
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).
Data collection: CrystalClear (Rigaku, 2005); cell
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).Fig. 1. The molecular structure of the title compound, drawn with 30% probability ellipsoids. |
C26H31NO3 | Z = 1 |
Mr = 405.52 | F(000) = 218 |
Triclinic, P1 | Dx = 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 |
Rigaku Saturn70 CCD diffractometer | 2588 independent reflections |
Radiation source: rotating anode | 1424 reflections with I > 2σ(I) |
Multilayer monochromator | Rint = 0.049 |
Detector resolution: 7.31 pixels mm-1 | θmax = 27.9°, θmin = 1.9° |
ω scans | h = −7→7 |
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005) | k = −11→10 |
Tmin = 0.988, Tmax = 0.992 | l = −14→14 |
5536 measured reflections |
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(Fo2) + (0.0499P)2] where P = (Fo2 + 2Fc2)/3 |
2588 reflections | (Δ/σ)max = 0.002 |
271 parameters | Δρmax = 0.18 e Å−3 |
3 restraints | Δρmin = −0.20 e Å−3 |
C26H31NO3 | γ = 101.23 (3)° |
Mr = 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)° |
Rigaku Saturn70 CCD diffractometer | 2588 independent reflections |
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005) | 1424 reflections with I > 2σ(I) |
Tmin = 0.988, Tmax = 0.992 | Rint = 0.049 |
5536 measured reflections |
R[F2 > 2σ(F2)] = 0.043 | 3 restraints |
wR(F2) = 0.106 | H-atom parameters constrained |
S = 0.89 | Δρmax = 0.18 e Å−3 |
2588 reflections | Δρmin = −0.20 e Å−3 |
271 parameters |
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 | ||
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* |
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) |
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 |
Mr | 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) |
Tmin, Tmax | 0.988, 0.992 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5536, 2588, 1424 |
Rint | 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 |
Δρmax, Δρmin (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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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°.