organic compounds
tert-Butyl 3-(3-methyl-1-oxidopyridin-1-ium-2-yl)benzoate
aUniversity of Innsbruck, Faculty of Chemistry and Pharmacy, Innrain 80, 6020 Innsbruck, Austria, bUniversity of Innsbruck, Institute of Mineralogy and Petrography, Innrain 52, 6020 Innsbruck, Austria, and cSandoz GmbH, Biochemiestrasse 10, 6250 Kundl, Austria
*Correspondence e-mail: gerhard.laus@uibk.ac.at
In the title compound, C17H19NO3, which was obtained by oxidation of the corresponding pyridine derivative, the dihedral angle between the benzene and the pyridine rings is 68.2 (1)°. In the crystal, C—H⋯O hydrogen bonds to carboxyl and N-oxide O-atom acceptors gives a cyclic dimer with an R22(18) motif which is extended into a undulating sheet structure lying parallel to (100) through weak C—H⋯Ooxide hydrogen bonds. Also present are π–π ring interactions [ring centroid separation = 3.561 (2) Å].
Keywords: crystal structure; hydrogen bonding; N-oxide; π–π ring interactions; lumacaftor.
CCDC reference: 1444673
Structure description
The title compound, C17H19NO3, is a key intermediate in the synthesis of the experimental drug lumacaftor for the therapy of cystic fibrosis (Norman, 2014; McColley, 2014).
The benzene and pyridine rings give a twisted conformation to the molecule (Fig. 1), with an interplanar dihedral angle of 68.2 (1)°. The carboxyl group is essentially coplanar with the benzene ring [torsion angle C12—C11—C14—O2 = −174.7 (2)°]. The methyl C atoms of the tert-butyl group display somewhat elongated ellipsoids which is not unusual for this group. In the crystal there is an absence of classic hydrogen bonding, but dual C—H⋯O hydrogen-bonding interactions to carboxyl and oxide O-atom acceptors (C12—H12⋯O2i and C4—H4⋯O1i, respectively; Table 1) give a cyclic dimer (Fig. 2), with an (18) motif (Bernstein et al., 1995). The cyclic aggregates are arranged in rows along c (Fig. 3), which are linked through weak C8—H8⋯O1ii hydrogen bonds, forming zigzag layered structures which lie parallel to (100) (Fig. 4). Similar hydrogen-bonding contacts have been observed in other pyridine oxides (McKay et al., 2006; Babu et al., 2007; Bowers et al., 2005). Present also in the crystal are π–π ring interactions between inversion-related pyridine rings [ring centroid separation = 3.561 (2) Å].
Synthesis and crystallization
The title compound was synthesized by stirring 2-(3-(tert-butoxycarbonyl)phenyl)-3-methylpyridine (Siesel, 2009) and m-chloroperoxybenzoic acid in dichloromethane. The mixture was treated with solid sodium sulfite, potassium carbonate and magnesium sulfate and the solvent was removed (Bremner et al., 1997). The resulting viscous oil crystallized after two weeks at room temperature giving the title compound (m.p. 352–354 K).
1H NMR (DMSO-d6, 300 MHz): δ 1.54 (s, 9H), 2.03 (s, 3H), 7.34–7.38 (m, 2H), 7.57–7.65 (m, 2H), 7.85 (s, 1H), 7.97 (d, J = 7.1 Hz, 1H), 8.23 (d, J = 5.3 Hz, 1H) p.p.m. 13C NMR (DMSO-d6, 75 MHz): δ 19.3 (CH3), 27.7 (3 CH3), 80.9 (C), 124.9 (CH), 127.1 (CH), 128.8 (CH), 129.1 (CH), 130.1 (CH), 131.6 (C), 132.8 (C), 134.0 (CH), 135.5 (C), 137.1 (CH), 147.5 (C), 164.6 (C=O) p.p.m. IR (neat): ν 3066, 2975, 2931, 1411, 1366, 1312, 1254, 1230, 1161, 1118, 1082, 1050, 959, 850, 787, 757, 738, 698, 569 cm−1.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 1444673
10.1107/S2414314615024906/zs2359sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S2414314615024906/zs2359Isup2.hkl
Supporting information file. DOI: 10.1107/S2414314615024906/zs2359Isup3.mol
Supporting information file. DOI: 10.1107/S2414314615024906/zs2359Isup4.cml
The title compound was synthesized by stirring 2-(3-(tert-butoxycarbonyl)phenyl)-3-methylpyridine (Siesel, 2009) and m-chloroperoxybenzoic acid in dichloromethane. The mixture was treated with solid sodium sulfite, potassium carbonate and magnesium sulfate and the solvent was removed (Bremner et al., 1997). The resulting viscous oil crystallized after two weeks at room temperature giving the title compound (m.p. 352–354 K).
1H NMR (DMSO-d6, 300 MHz): δ 1.54 (s, 9H), 2.03 (s, 3H), 7.34–7.38 (m, 2H), 7.57–7.65 (m, 2H), 7.85 (s, 1H), 7.97 (d, J = 7.1 Hz, 1H), 8.23 (d, J = 5.3 Hz, 1H) p.p.m. 13C NMR (DMSO-d6, 75 MHz): δ 19.3 (CH3), 27.7 (3 CH3), 80.9 (C), 124.9 (CH), 127.1 (CH), 128.8 (CH), 129.1 (CH), 130.1 (CH), 131.6 (C), 132.8 (C), 134.0 (CH), 135.5 (C), 137.1 (CH), 147.5 (C), 164.6 (C═O) p.p.m. IR (neat): ν 3066, 2975, 2931, 1411, 1366, 1312, 1254, 1230, 1161, 1118, 1082, 1050, 959, 850, 787, 757, 738, 698, 569 cm−1.
The title compound, C17H19NO3, is a key intermediate in the synthesis of the experimental drug lumacaftor for the therapy of cystic fibrosis (Norman, 2014; McColley, 2014).
The benzene and pyridine rings give a twisted conformation to the molecule (Fig. 1), with an interplanar dihedral angle of 68.2 (1)°. The carboxyl group is essentially coplanar with the benzene ring [torsion angle C12—C11—C14—O2 = −174.7 (2)°]. The methyl C atoms of the tert-butyl group display somewhat elongated ellipsoids which is not unusual for this group. In the crystal there is an absence of classic hydrogen bonding, but dual C—H···O hydrogen-bonding interactions to carboxyl and oxide O-atom acceptors (C12—H12···O2i and C4—H4···O1i, respectively; Table 1) give a cyclic dimer π–π ring interactions between inversion-related pyridine rings [ring centroid separation = 3.561 (2) Å].
(Fig. 2), with an R22(18) motif (Bernstein et al., 1995). The cyclic aggregates are arranged in rows along c (Fig. 3), which are linked through weak C8—H8···O1ii hydrogen bonds, forming zigzag layered structures which lie parallel to (100) (Fig. 4). Similar hydrogen-bonding contacts have been observed in other pyridine oxides (McKay et al., 2006; Babu et al., 2007; Bowers et al., 2005). Present also in the crystal areData collection: CrysAlis PRO (Agilent, 2014); cell
CrysAlis PRO (Agilent, 2014); data reduction: CrysAlis PRO (Agilent, 2014); program(s) used to solve structure: SIR2002 (Burla et al., 2003); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); software used to prepare material for publication: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2006).Fig. 1. The molecular structure of the title compound, with atom labels and 50% probability displacement ellipsoids for non-H atoms. | |
Fig. 2. Short C—H···O and π–π contacts in the crystal structure of the title compound. H atoms engaged in hydrogen bonding are drawn as spheres and all other H atoms are omitted. Symmetry code: (iii) −x + 1, −y, −z + 1. For other codes, see Table 1. | |
Fig. 3. Rows of cyclic hydrogen-bond aggregates along along c. | |
Fig. 4. The undulating sheet structure extending along the general b-axis direction. |
C17H19NO3 | F(000) = 608 |
Mr = 285.33 | Dx = 1.243 Mg m−3 |
Monoclinic, P21/c | Melting point = 352–354 K |
Hall symbol: -P 2ybc | Cu Kα radiation, λ = 1.54184 Å |
a = 13.6690 (7) Å | Cell parameters from 3088 reflections |
b = 10.8170 (6) Å | θ = 3.4–66.0° |
c = 10.9271 (7) Å | µ = 0.69 mm−1 |
β = 109.365 (7)° | T = 173 K |
V = 1524.25 (16) Å3 | Prismatic fragment, colourless |
Z = 4 | 0.16 × 0.11 × 0.1 mm |
Agilent Xcalibur, Ruby, Gemini ultra diffractometer | 2730 independent reflections |
Radiation source: sealed X-ray tube | 1984 reflections with I > 2σ(I) |
Mirror monochromator | Rint = 0.066 |
Detector resolution: 10.3575 pixels mm-1 | θmax = 67.7°, θmin = 3.4° |
ω scans | h = −16→13 |
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014) | k = −12→12 |
Tmin = 0.884, Tmax = 1 | l = −13→12 |
15403 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)] = 0.053 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.158 | H-atom parameters constrained |
S = 1.04 | w = 1/[σ2(Fo2) + (0.0816P)2 + 0.290P] where P = (Fo2 + 2Fc2)/3 |
2730 reflections | (Δ/σ)max < 0.001 |
194 parameters | Δρmax = 0.19 e Å−3 |
0 restraints | Δρmin = −0.20 e Å−3 |
C17H19NO3 | V = 1524.25 (16) Å3 |
Mr = 285.33 | Z = 4 |
Monoclinic, P21/c | Cu Kα radiation |
a = 13.6690 (7) Å | µ = 0.69 mm−1 |
b = 10.8170 (6) Å | T = 173 K |
c = 10.9271 (7) Å | 0.16 × 0.11 × 0.1 mm |
β = 109.365 (7)° |
Agilent Xcalibur, Ruby, Gemini ultra diffractometer | 2730 independent reflections |
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014) | 1984 reflections with I > 2σ(I) |
Tmin = 0.884, Tmax = 1 | Rint = 0.066 |
15403 measured reflections |
R[F2 > 2σ(F2)] = 0.053 | 0 restraints |
wR(F2) = 0.158 | H-atom parameters constrained |
S = 1.04 | Δρmax = 0.19 e Å−3 |
2730 reflections | Δρmin = −0.20 e Å−3 |
194 parameters |
Experimental. Absorption correction: CrysAlis PRO (Agilent, 2014). Agilent Technologies, Version 1.171.37.31 (release 14–01-2014 CrysAlis171. NET) (compiled Jan 14 2014,18:38:05) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. |
Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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 | ||
O3 | 0.10663 (13) | 0.27239 (17) | 0.77336 (16) | 0.0605 (5) | |
O2 | 0.13706 (12) | 0.21671 (17) | 0.97944 (16) | 0.0562 (5) | |
O1 | 0.43812 (13) | 0.23977 (15) | 0.67190 (18) | 0.0573 (5) | |
N2 | 0.40653 (13) | 0.15378 (17) | 0.58465 (19) | 0.0442 (5) | |
C11 | 0.23596 (14) | 0.12519 (18) | 0.86088 (19) | 0.0367 (5) | |
C12 | 0.26102 (14) | 0.12596 (18) | 0.7478 (2) | 0.0362 (5) | |
H12 | 0.2256 | 0.1801 | 0.6788 | 0.043* | |
C9 | 0.36423 (15) | −0.0318 (2) | 0.9494 (2) | 0.0464 (5) | |
H9 | 0.3995 | −0.0859 | 1.0184 | 0.056* | |
C7 | 0.33842 (14) | 0.04709 (19) | 0.7351 (2) | 0.0383 (5) | |
C10 | 0.28839 (15) | 0.0467 (2) | 0.9625 (2) | 0.0423 (5) | |
H10 | 0.2721 | 0.0471 | 1.0405 | 0.051* | |
C1 | 0.36110 (14) | 0.04809 (19) | 0.6119 (2) | 0.0407 (5) | |
C8 | 0.38909 (15) | −0.0320 (2) | 0.8361 (2) | 0.0444 (5) | |
H8 | 0.441 | −0.0865 | 0.8277 | 0.053* | |
C14 | 0.15541 (15) | 0.20928 (19) | 0.8791 (2) | 0.0387 (5) | |
C6 | 0.33577 (16) | −0.0479 (2) | 0.5220 (2) | 0.0474 (5) | |
C5 | 0.35176 (17) | −0.0325 (3) | 0.4037 (2) | 0.0563 (6) | |
H5 | 0.3352 | −0.0976 | 0.3419 | 0.068* | |
C3 | 0.41890 (16) | 0.1679 (2) | 0.4671 (2) | 0.0507 (6) | |
H3 | 0.4472 | 0.2428 | 0.448 | 0.061* | |
C15 | 0.02417 (19) | 0.3638 (2) | 0.7682 (2) | 0.0550 (6) | |
C4 | 0.39149 (17) | 0.0768 (3) | 0.3761 (2) | 0.0556 (6) | |
H4 | 0.3997 | 0.0887 | 0.2939 | 0.067* | |
C13 | 0.2918 (2) | −0.1661 (2) | 0.5543 (3) | 0.0640 (7) | |
H13A | 0.2693 | −0.2192 | 0.4773 | 0.096* | |
H13B | 0.2323 | −0.1472 | 0.5822 | 0.096* | |
H13C | 0.3451 | −0.2089 | 0.6243 | 0.096* | |
C16 | −0.0668 (2) | 0.2999 (3) | 0.7882 (4) | 0.0834 (10) | |
H16A | −0.1239 | 0.3589 | 0.7744 | 0.125* | |
H16B | −0.0467 | 0.2675 | 0.8768 | 0.125* | |
H16C | −0.0894 | 0.2316 | 0.7263 | 0.125* | |
C17 | 0.0654 (2) | 0.4624 (3) | 0.8682 (4) | 0.0920 (12) | |
H17A | 0.129 | 0.4971 | 0.8596 | 0.138* | |
H17B | 0.0806 | 0.4267 | 0.955 | 0.138* | |
H17C | 0.0135 | 0.528 | 0.8556 | 0.138* | |
C18 | −0.0024 (4) | 0.4125 (6) | 0.6342 (4) | 0.165 (3) | |
H18A | 0.0609 | 0.4401 | 0.6191 | 0.248* | |
H18B | −0.0502 | 0.4825 | 0.6229 | 0.248* | |
H18C | −0.0356 | 0.3473 | 0.5721 | 0.248* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O3 | 0.0708 (11) | 0.0713 (11) | 0.0529 (10) | 0.0386 (9) | 0.0385 (8) | 0.0204 (8) |
O2 | 0.0531 (9) | 0.0745 (12) | 0.0468 (9) | 0.0113 (8) | 0.0244 (7) | 0.0025 (8) |
O1 | 0.0585 (10) | 0.0479 (9) | 0.0741 (11) | −0.0125 (7) | 0.0335 (8) | −0.0086 (9) |
N2 | 0.0360 (9) | 0.0454 (10) | 0.0567 (11) | 0.0049 (7) | 0.0228 (8) | 0.0012 (9) |
C11 | 0.0303 (9) | 0.0366 (10) | 0.0434 (11) | −0.0046 (8) | 0.0127 (8) | 0.0008 (9) |
C12 | 0.0314 (9) | 0.0351 (10) | 0.0436 (11) | −0.0008 (8) | 0.0145 (8) | 0.0011 (9) |
C9 | 0.0358 (10) | 0.0452 (12) | 0.0534 (13) | 0.0003 (9) | 0.0084 (9) | 0.0118 (10) |
C7 | 0.0314 (9) | 0.0368 (10) | 0.0482 (12) | −0.0021 (8) | 0.0151 (8) | −0.0014 (9) |
C10 | 0.0342 (10) | 0.0456 (12) | 0.0462 (12) | −0.0058 (9) | 0.0122 (9) | 0.0053 (10) |
C1 | 0.0290 (9) | 0.0414 (11) | 0.0535 (13) | 0.0075 (8) | 0.0163 (9) | 0.0025 (10) |
C8 | 0.0325 (10) | 0.0405 (12) | 0.0584 (14) | 0.0031 (8) | 0.0126 (9) | 0.0040 (10) |
C14 | 0.0349 (10) | 0.0416 (11) | 0.0414 (12) | −0.0049 (8) | 0.0150 (9) | −0.0008 (9) |
C6 | 0.0381 (10) | 0.0475 (12) | 0.0578 (14) | 0.0077 (9) | 0.0177 (10) | −0.0038 (11) |
C5 | 0.0464 (12) | 0.0679 (16) | 0.0557 (14) | 0.0099 (11) | 0.0185 (11) | −0.0111 (13) |
C3 | 0.0404 (11) | 0.0578 (14) | 0.0605 (15) | 0.0124 (10) | 0.0255 (11) | 0.0132 (12) |
C15 | 0.0586 (14) | 0.0583 (14) | 0.0602 (14) | 0.0281 (11) | 0.0360 (12) | 0.0115 (12) |
C4 | 0.0412 (11) | 0.0764 (18) | 0.0542 (14) | 0.0150 (11) | 0.0224 (10) | 0.0082 (13) |
C13 | 0.0694 (16) | 0.0486 (14) | 0.0786 (18) | −0.0065 (12) | 0.0306 (14) | −0.0162 (13) |
C16 | 0.0440 (13) | 0.0639 (18) | 0.132 (3) | 0.0037 (12) | 0.0153 (16) | −0.0009 (18) |
C17 | 0.0592 (16) | 0.0502 (16) | 0.160 (3) | 0.0044 (13) | 0.0279 (19) | −0.0169 (19) |
C18 | 0.219 (5) | 0.216 (6) | 0.103 (3) | 0.184 (5) | 0.111 (3) | 0.098 (3) |
O3—C14 | 1.317 (3) | C5—C4 | 1.376 (4) |
O3—C15 | 1.487 (3) | C5—H5 | 0.95 |
O2—C14 | 1.206 (3) | C3—C4 | 1.361 (4) |
O1—N2 | 1.299 (2) | C3—H3 | 0.95 |
N2—C3 | 1.359 (3) | C15—C18 | 1.483 (4) |
N2—C1 | 1.380 (3) | C15—C17 | 1.497 (4) |
C11—C12 | 1.387 (3) | C15—C16 | 1.501 (4) |
C11—C10 | 1.393 (3) | C4—H4 | 0.95 |
C11—C14 | 1.491 (3) | C13—H13A | 0.98 |
C12—C7 | 1.401 (3) | C13—H13B | 0.98 |
C12—H12 | 0.95 | C13—H13C | 0.98 |
C9—C10 | 1.383 (3) | C16—H16A | 0.98 |
C9—C8 | 1.388 (3) | C16—H16B | 0.98 |
C9—H9 | 0.95 | C16—H16C | 0.98 |
C7—C8 | 1.386 (3) | C17—H17A | 0.98 |
C7—C1 | 1.479 (3) | C17—H17B | 0.98 |
C10—H10 | 0.95 | C17—H17C | 0.98 |
C1—C6 | 1.392 (3) | C18—H18A | 0.98 |
C8—H8 | 0.95 | C18—H18B | 0.98 |
C6—C5 | 1.390 (3) | C18—H18C | 0.98 |
C6—C13 | 1.504 (4) | ||
C14—O3—C15 | 122.35 (17) | N2—C3—H3 | 119.4 |
O1—N2—C3 | 119.87 (19) | C4—C3—H3 | 119.4 |
O1—N2—C1 | 119.92 (18) | C18—C15—O3 | 102.03 (19) |
C3—N2—C1 | 120.2 (2) | C18—C15—C17 | 112.2 (3) |
C12—C11—C10 | 120.00 (18) | O3—C15—C17 | 110.4 (2) |
C12—C11—C14 | 121.76 (18) | C18—C15—C16 | 111.3 (4) |
C10—C11—C14 | 118.22 (19) | O3—C15—C16 | 110.0 (2) |
C11—C12—C7 | 120.12 (19) | C17—C15—C16 | 110.6 (2) |
C11—C12—H12 | 119.9 | C3—C4—C5 | 119.7 (2) |
C7—C12—H12 | 119.9 | C3—C4—H4 | 120.2 |
C10—C9—C8 | 120.4 (2) | C5—C4—H4 | 120.2 |
C10—C9—H9 | 119.8 | C6—C13—H13A | 109.5 |
C8—C9—H9 | 119.8 | C6—C13—H13B | 109.5 |
C8—C7—C12 | 119.43 (19) | H13A—C13—H13B | 109.5 |
C8—C7—C1 | 121.94 (18) | C6—C13—H13C | 109.5 |
C12—C7—C1 | 118.60 (18) | H13A—C13—H13C | 109.5 |
C9—C10—C11 | 119.8 (2) | H13B—C13—H13C | 109.5 |
C9—C10—H10 | 120.1 | C15—C16—H16A | 109.5 |
C11—C10—H10 | 120.1 | C15—C16—H16B | 109.5 |
N2—C1—C6 | 119.4 (2) | H16A—C16—H16B | 109.5 |
N2—C1—C7 | 116.60 (18) | C15—C16—H16C | 109.5 |
C6—C1—C7 | 124.0 (2) | H16A—C16—H16C | 109.5 |
C7—C8—C9 | 120.21 (19) | H16B—C16—H16C | 109.5 |
C7—C8—H8 | 119.9 | C15—C17—H17A | 109.5 |
C9—C8—H8 | 119.9 | C15—C17—H17B | 109.5 |
O2—C14—O3 | 124.45 (19) | H17A—C17—H17B | 109.5 |
O2—C14—C11 | 123.18 (19) | C15—C17—H17C | 109.5 |
O3—C14—C11 | 112.37 (18) | H17A—C17—H17C | 109.5 |
C5—C6—C1 | 119.2 (2) | H17B—C17—H17C | 109.5 |
C5—C6—C13 | 121.2 (2) | C15—C18—H18A | 109.5 |
C1—C6—C13 | 119.6 (2) | C15—C18—H18B | 109.5 |
C4—C5—C6 | 120.1 (2) | H18A—C18—H18B | 109.5 |
C4—C5—H5 | 119.9 | C15—C18—H18C | 109.5 |
C6—C5—H5 | 119.9 | H18A—C18—H18C | 109.5 |
N2—C3—C4 | 121.3 (2) | H18B—C18—H18C | 109.5 |
C10—C11—C12—C7 | 0.6 (3) | C15—O3—C14—C11 | −179.0 (2) |
C14—C11—C12—C7 | 178.89 (18) | C12—C11—C14—O2 | −174.72 (19) |
C11—C12—C7—C8 | 0.4 (3) | C10—C11—C14—O2 | 3.6 (3) |
C11—C12—C7—C1 | 178.40 (17) | C12—C11—C14—O3 | 6.0 (3) |
C8—C9—C10—C11 | 0.6 (3) | C10—C11—C14—O3 | −175.61 (18) |
C12—C11—C10—C9 | −1.1 (3) | N2—C1—C6—C5 | −3.4 (3) |
C14—C11—C10—C9 | −179.44 (19) | C7—C1—C6—C5 | 173.95 (18) |
O1—N2—C1—C6 | −174.47 (18) | N2—C1—C6—C13 | 176.57 (19) |
C3—N2—C1—C6 | 5.1 (3) | C7—C1—C6—C13 | −6.1 (3) |
O1—N2—C1—C7 | 8.0 (3) | C1—C6—C5—C4 | −0.5 (3) |
C3—N2—C1—C7 | −172.40 (17) | C13—C6—C5—C4 | 179.6 (2) |
C8—C7—C1—N2 | −113.6 (2) | O1—N2—C3—C4 | 176.59 (19) |
C12—C7—C1—N2 | 68.4 (2) | C1—N2—C3—C4 | −3.0 (3) |
C8—C7—C1—C6 | 68.9 (3) | C14—O3—C15—C18 | 177.7 (4) |
C12—C7—C1—C6 | −109.0 (2) | C14—O3—C15—C17 | 58.2 (3) |
C12—C7—C8—C9 | −0.9 (3) | C14—O3—C15—C16 | −64.1 (3) |
C1—C7—C8—C9 | −178.79 (19) | N2—C3—C4—C5 | −0.9 (3) |
C10—C9—C8—C7 | 0.4 (3) | C6—C5—C4—C3 | 2.6 (3) |
C15—O3—C14—O2 | 1.8 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
C4—H4···O1i | 0.95 | 2.44 | 3.204 (3) | 137 |
C12—H12···O2i | 0.95 | 2.39 | 3.327 (2) | 169 |
C8—H8···O1ii | 0.95 | 2.50 | 3.438 (3) | 169 |
Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x+1, y−1/2, −z+3/2. |
D—H···A | D—H | H···A | D···A | D—H···A |
C4—H4···O1i | 0.95 | 2.44 | 3.204 (3) | 137 |
C12—H12···O2i | 0.95 | 2.39 | 3.327 (2) | 169 |
C8—H8···O1ii | 0.95 | 2.50 | 3.438 (3) | 169 |
Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x+1, y−1/2, −z+3/2. |
Experimental details
Crystal data | |
Chemical formula | C17H19NO3 |
Mr | 285.33 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 173 |
a, b, c (Å) | 13.6690 (7), 10.8170 (6), 10.9271 (7) |
β (°) | 109.365 (7) |
V (Å3) | 1524.25 (16) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.69 |
Crystal size (mm) | 0.16 × 0.11 × 0.1 |
Data collection | |
Diffractometer | Agilent Xcalibur, Ruby, Gemini ultra |
Absorption correction | Multi-scan (CrysAlis PRO; Agilent, 2014) |
Tmin, Tmax | 0.884, 1 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 15403, 2730, 1984 |
Rint | 0.066 |
(sin θ/λ)max (Å−1) | 0.600 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.053, 0.158, 1.04 |
No. of reflections | 2730 |
No. of parameters | 194 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.19, −0.20 |
Computer programs: CrysAlis PRO (Agilent, 2014), CrysAlis PRO (Agilent, 2014), SIR2002 (Burla et al., 2003), SHELXL2014 (Sheldrick, 2015), ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2006).
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
The title compound, C17H19NO3, is a key intermediate in the synthesis of the experimental drug lumacaftor for the therapy of cystic fibrosis (Norman, 2014; McColley, 2014).
In the crystal structure of this compound (Fig. 1), the benzene and pyridine rings give a twisted conformation to the molecule, with an interplanar dihedral angle of 68.2 (1)°. The carboxyl group is essentially coplanar with the benzene ring [torsion angle C12—C11—C14—O2 = −174.7 (2)°]. The methyl C atoms of the tert-butyl group display somewhat elongated ellipsoids which is not unusual for this group. In the crystal there is an absence of classic hydrogen-bonding, but dual C—H···O hydrogen bonding interactions to carboxyl and oxide O-atom acceptors [C12—H···O2i and C4—H···O1i, respectively] (Table 1) give a cyclic dimer substructure (Fig. 2), with an R22(18) motif (Bernstein et al., 1995). The cyclic aggregates are arranged in rows along c (Fig. 3) which are linked through weak C8—H···O1ii hydrogen bonds, forming zigzag layered structures which lie parallel to (100) (Fig. 4). Similar hydrogen-bonding contacts have been observed in other pyridine oxides (McKay et al., 2006; Babu et al., 2007; Bowers et al., 2005). Present also in the crystal are π–π ring interactions between inversion-related pyridine rings [ring centroid separation = 3.561 (2) Å].