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Acta Crystallogr Sect E Struct Rep Online. 2008 November 1; 64(Pt 11): o2214.
Published online 2008 October 31. doi:  10.1107/S1600536808034715
PMCID: PMC2959496

Ethyl 1-cyclo­propyl-6,7-difluoro-8-meth­oxy-4-oxo-1,4-dihydro­quinoline-3-carboxyl­ate

Abstract

In the title compound, C16H15F2NO4, the dihedral angle between the three-membered ring and the quinoline ring system is 64.3 (3)°. In the crystal structure, inter­molecular C—H(...)O hydrogen bonds link the mol­ecules, forming a column running along [101].

Related literature

The title compound is a key inter­mediate in the synthesis of a series of fluoro­quinolones, see: Matsumoto et al. (1996 [triangle]); Nagano et al. (1989 [triangle]); Petersen et al. (1993 [triangle]).

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Object name is e-64-o2214-scheme1.jpg

Experimental

Crystal data

  • C16H15F2NO4
  • M r = 323.29
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o2214-efi1.jpg
  • a = 16.395 (3) Å
  • b = 17.732 (4) Å
  • c = 12.199 (2) Å
  • β = 123.71 (3)°
  • V = 2950.1 (14) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.12 mm−1
  • T = 293 (2) K
  • 0.10 × 0.10 × 0.05 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (North et al., 1968 [triangle]) T min = 0.988, T max = 0.994
  • 2760 measured reflections
  • 2663 independent reflections
  • 1580 reflections with I > 2σ(I)
  • R int = 0.068
  • 3 standard reflections every 200 reflections intensity decay: none

Refinement

  • R[F 2 > 2σ(F 2)] = 0.061
  • wR(F 2) = 0.175
  • S = 1.04
  • 2663 reflections
  • 208 parameters
  • H-atom parameters constrained
  • Δρmax = 0.21 e Å−3
  • Δρmin = −0.19 e Å−3

Data collection: CAD-4 Software (Enraf–Nonius, 1989 [triangle]); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: PLATON (Spek, 2003 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808034715/is2351sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808034715/is2351Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Comment

The title compound, 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid ethyl ester, is a key intermediate to synthesize a series of fluoroquinolones,such as moxifloxacin (Petersen et al., 1993), balofloxacin (Nagano et al., 1989) and gatifloxacin (Matsumoto et al., 1996). As part of our studies in this area, we report here the synthesis and crystal structure of the title compound, (I) (Fig. 1).

The benzene ring and its adjacent six-membered ring were almost coplanar. The dihedral angles between the three-membered ring and the benzene ring is 65.30 (14)°. In the crystal structure, intermolecular C—H···O hydrogen bonds link the molecules, in which they are effective in the stabilization of the structure.

Experimental

A solution of 26 g (0.075 mol) of 3-cyclopropylamino-2- (2,4,5-trifluoro-3-methoxybenzoyl)acrylic acid ethyl ester and 110 ml of DMF was treated with 22 g (0.16 mol) of K2CO3, and then heated to 50 °C with stirring for 1 h. The resulting precipitate was filtered, washed with the mixture of ice and water, and dried to give 23 g of the title compound (yield 95%). Crystals of (I) suitable for X-ray diffraction were obtained by slow evaporation of a methanol solution.

Refinement

All H atoms were placed geometrically (C—H = 0.93–0.98 Å) and refined as riding, with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C).

Figures

Fig. 1.
The molecular structure of the title compound, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.

Crystal data

C16H15F2NO4F(000) = 1344
Mr = 323.29Dx = 1.456 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2ycCell parameters from 25 reflections
a = 16.395 (3) Åθ = 9–12°
b = 17.732 (4) ŵ = 0.12 mm1
c = 12.199 (2) ÅT = 293 K
β = 123.71 (3)°Block, colorless
V = 2950.1 (14) Å30.10 × 0.10 × 0.05 mm
Z = 8

Data collection

Enraf–Nonius CAD-4 diffractometer1580 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.068
graphiteθmax = 25.2°, θmin = 1.9°
ω/2θ scansh = −2→19
Absorption correction: ψ scan (North et al., 1968)k = 0→21
Tmin = 0.988, Tmax = 0.994l = −14→12
2760 measured reflections3 standard reflections every 200 reflections
2663 independent reflections intensity decay: none

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.061H-atom parameters constrained
wR(F2) = 0.175w = 1/[σ2(Fo2) + (0.06P)2 + 5P] where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max < 0.001
2663 reflectionsΔρmax = 0.21 e Å3
208 parametersΔρmin = −0.19 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008)
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0026 (5)

Special details

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)

xyzUiso*/Ueq
N0.1306 (2)0.28705 (16)−0.2762 (2)0.0512 (7)
O10.1226 (2)0.17328 (16)−0.4536 (2)0.0752 (8)
F10.1209 (2)−0.01688 (12)−0.1874 (3)0.1108 (10)
C10.0365 (4)0.1548 (3)−0.5789 (4)0.1079 (18)
H1A−0.00940.1957−0.60880.162*
H1B0.00720.1100−0.57090.162*
H1C0.05390.1462−0.64120.162*
O20.1328 (2)0.21459 (14)0.0430 (2)0.0736 (8)
F20.1196 (2)0.02669 (13)−0.3966 (3)0.0991 (9)
C20.1223 (2)0.1543 (2)−0.3446 (3)0.0550 (9)
O30.1010 (3)0.44539 (16)−0.0591 (3)0.0988 (11)
C30.1211 (3)0.0799 (2)−0.3166 (4)0.0664 (10)
O40.11605 (19)0.36229 (14)0.0869 (2)0.0666 (7)
C40.1229 (3)0.0575 (2)−0.2074 (4)0.0689 (10)
C50.1266 (3)0.1091 (2)−0.1231 (4)0.0604 (9)
H5A0.12740.0935−0.04970.073*
C60.1292 (2)0.18552 (18)−0.1466 (3)0.0462 (8)
C70.1284 (2)0.20942 (18)−0.2564 (3)0.0447 (8)
C80.1282 (2)0.23918 (19)−0.0548 (3)0.0466 (8)
C90.1211 (2)0.31671 (18)−0.0906 (3)0.0450 (8)
C100.1234 (2)0.33541 (19)−0.1976 (3)0.0520 (8)
H10A0.11960.3864−0.21760.062*
C110.1438 (3)0.3184 (2)−0.3768 (3)0.0650 (11)
H11A0.08540.3183−0.46720.078*
C120.2375 (3)0.3084 (2)−0.3630 (4)0.0737 (11)
H12A0.23620.3011−0.44280.088*
H12B0.28850.2807−0.28690.088*
C130.2109 (3)0.3841 (2)−0.3402 (4)0.0821 (13)
H13A0.19280.4227−0.40630.098*
H13B0.24520.4024−0.25020.098*
C140.1107 (3)0.3813 (2)−0.0227 (3)0.0551 (9)
C150.1052 (3)0.4226 (2)0.1578 (4)0.0711 (11)
H15A0.03950.44350.10500.085*
H15B0.15170.46260.17700.085*
C160.1232 (4)0.3914 (3)0.2797 (4)0.0988 (16)
H16A0.11720.43060.32910.148*
H16B0.18820.37060.33080.148*
H16C0.07620.35240.25950.148*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N0.0654 (18)0.0554 (18)0.0445 (15)0.0109 (13)0.0378 (14)0.0036 (13)
O10.097 (2)0.087 (2)0.0541 (15)−0.0087 (15)0.0494 (15)−0.0196 (13)
F10.182 (3)0.0485 (14)0.160 (3)−0.0203 (15)0.131 (2)−0.0184 (15)
C10.110 (4)0.158 (5)0.060 (3)0.008 (3)0.049 (3)−0.025 (3)
O20.122 (2)0.0632 (16)0.0624 (16)−0.0063 (15)0.0677 (17)−0.0018 (13)
F20.144 (2)0.0714 (16)0.119 (2)−0.0169 (15)0.0963 (19)−0.0394 (14)
C20.051 (2)0.070 (3)0.0504 (19)0.0013 (17)0.0323 (16)−0.0102 (17)
O30.189 (3)0.0569 (18)0.101 (2)0.0292 (19)0.112 (2)0.0115 (16)
C30.076 (3)0.061 (2)0.075 (2)−0.0102 (19)0.050 (2)−0.029 (2)
O40.105 (2)0.0581 (15)0.0640 (15)0.0071 (13)0.0637 (15)−0.0046 (12)
C40.083 (3)0.048 (2)0.097 (3)−0.0039 (19)0.063 (2)−0.003 (2)
C50.072 (2)0.054 (2)0.073 (2)−0.0034 (18)0.052 (2)−0.0022 (19)
C60.0426 (17)0.053 (2)0.0471 (17)−0.0039 (15)0.0275 (15)−0.0054 (15)
C70.0370 (16)0.055 (2)0.0448 (17)0.0004 (14)0.0242 (14)−0.0072 (14)
C80.0433 (17)0.059 (2)0.0429 (17)−0.0052 (15)0.0273 (14)−0.0085 (15)
C90.0409 (17)0.058 (2)0.0382 (15)0.0037 (14)0.0234 (13)−0.0034 (15)
C100.063 (2)0.052 (2)0.0487 (18)0.0101 (16)0.0359 (17)−0.0017 (16)
C110.100 (3)0.066 (2)0.0420 (18)0.020 (2)0.047 (2)0.0113 (17)
C120.106 (3)0.072 (3)0.079 (3)0.010 (2)0.074 (3)0.006 (2)
C130.143 (4)0.060 (3)0.084 (3)0.005 (3)0.089 (3)0.009 (2)
C140.072 (2)0.057 (2)0.0516 (19)0.0087 (18)0.0432 (18)0.0020 (17)
C150.107 (3)0.064 (2)0.071 (2)0.012 (2)0.068 (2)−0.0086 (19)
C160.145 (4)0.099 (4)0.092 (3)0.014 (3)0.091 (3)−0.011 (3)

Geometric parameters (Å, °)

N—C101.340 (4)C6—C71.398 (4)
N—C71.402 (4)C6—C81.477 (4)
N—C111.468 (4)C8—C91.428 (4)
O1—C21.373 (4)C9—C101.367 (4)
O1—C11.429 (5)C9—C141.479 (4)
F1—C41.345 (4)C10—H10A0.9300
C1—H1A0.9600C11—C121.462 (5)
C1—H1B0.9600C11—C131.491 (6)
C1—H1C0.9600C11—H11A0.9800
O2—C81.233 (4)C12—C131.485 (5)
F2—C31.348 (4)C12—H12A0.9700
C2—C31.365 (5)C12—H12B0.9700
C2—C71.416 (4)C13—H13A0.9700
O3—C141.198 (4)C13—H13B0.9700
C3—C41.374 (5)C15—C161.455 (5)
O4—C141.333 (4)C15—H15A0.9700
O4—C151.448 (4)C15—H15B0.9700
C4—C51.353 (5)C16—H16A0.9600
C5—C61.391 (5)C16—H16B0.9600
C5—H5A0.9300C16—H16C0.9600
C10—N—C7119.0 (3)N—C10—H10A117.0
C10—N—C11117.9 (3)C9—C10—H10A117.0
C7—N—C11123.1 (3)C12—C11—N119.4 (3)
C2—O1—C1116.6 (3)C12—C11—C1360.4 (3)
O1—C1—H1A109.5N—C11—C13118.2 (3)
O1—C1—H1B109.5C12—C11—H11A115.8
H1A—C1—H1B109.5N—C11—H11A115.8
O1—C1—H1C109.5C13—C11—H11A115.8
H1A—C1—H1C109.5C11—C12—C1360.8 (3)
H1B—C1—H1C109.5C11—C12—H12A117.7
C3—C2—O1119.2 (3)C13—C12—H12A117.7
C3—C2—C7118.8 (3)C11—C12—H12B117.7
O1—C2—C7122.0 (3)C13—C12—H12B117.7
F2—C3—C2119.5 (3)H12A—C12—H12B114.8
F2—C3—C4118.7 (4)C12—C13—C1158.8 (3)
C2—C3—C4121.8 (3)C12—C13—H13A117.9
C14—O4—C15116.7 (3)C11—C13—H13A117.9
F1—C4—C5121.3 (4)C12—C13—H13B117.9
F1—C4—C3118.1 (4)C11—C13—H13B117.9
C5—C4—C3120.6 (4)H13A—C13—H13B115.0
C4—C5—C6119.7 (3)O3—C14—O4122.2 (3)
C4—C5—H5A120.1O3—C14—C9124.0 (3)
C6—C5—H5A120.1O4—C14—C9113.7 (3)
C5—C6—C7120.5 (3)O4—C15—C16107.8 (3)
C5—C6—C8117.2 (3)O4—C15—H15A110.1
C7—C6—C8122.2 (3)C16—C15—H15A110.1
C6—C7—N118.4 (3)O4—C15—H15B110.1
C6—C7—C2118.6 (3)C16—C15—H15B110.1
N—C7—C2123.0 (3)H15A—C15—H15B108.5
O2—C8—C9126.0 (3)C15—C16—H16A109.5
O2—C8—C6119.1 (3)C15—C16—H16B109.5
C9—C8—C6115.0 (3)H16A—C16—H16B109.5
C10—C9—C8119.0 (3)C15—C16—H16C109.5
C10—C9—C14114.9 (3)H16A—C16—H16C109.5
C8—C9—C14126.2 (3)H16B—C16—H16C109.5
N—C10—C9126.0 (3)
C1—O1—C2—C366.2 (5)C5—C6—C8—O25.6 (4)
C1—O1—C2—C7−117.1 (4)C7—C6—C8—O2−177.2 (3)
O1—C2—C3—F2−0.4 (5)C5—C6—C8—C9−174.0 (3)
C7—C2—C3—F2−177.2 (3)C7—C6—C8—C93.1 (4)
O1—C2—C3—C4178.6 (3)O2—C8—C9—C10175.5 (3)
C7—C2—C3—C41.8 (6)C6—C8—C9—C10−4.9 (4)
F2—C3—C4—F1−1.4 (6)O2—C8—C9—C14−4.8 (5)
C2—C3—C4—F1179.6 (3)C6—C8—C9—C14174.8 (3)
F2—C3—C4—C5178.6 (3)C7—N—C10—C95.2 (5)
C2—C3—C4—C5−0.5 (6)C11—N—C10—C9−172.8 (3)
F1—C4—C5—C6179.6 (3)C8—C9—C10—N0.9 (5)
C3—C4—C5—C6−0.4 (6)C14—C9—C10—N−178.8 (3)
C4—C5—C6—C7−0.2 (5)C10—N—C11—C12110.6 (4)
C4—C5—C6—C8177.0 (3)C7—N—C11—C12−67.3 (5)
C5—C6—C7—N179.6 (3)C10—N—C11—C1340.6 (5)
C8—C6—C7—N2.6 (4)C7—N—C11—C13−137.3 (3)
C5—C6—C7—C21.6 (4)N—C11—C12—C13−107.7 (4)
C8—C6—C7—C2−175.5 (3)N—C11—C13—C12109.6 (4)
C10—N—C7—C6−6.7 (4)C15—O4—C14—O32.7 (5)
C11—N—C7—C6171.2 (3)C15—O4—C14—C9−179.2 (3)
C10—N—C7—C2171.3 (3)C10—C9—C14—O32.8 (5)
C11—N—C7—C2−10.8 (5)C8—C9—C14—O3−176.9 (4)
C3—C2—C7—C6−2.3 (5)C10—C9—C14—O4−175.2 (3)
O1—C2—C7—C6−179.0 (3)C8—C9—C14—O45.1 (5)
C3—C2—C7—N179.7 (3)C14—O4—C15—C16−174.3 (3)
O1—C2—C7—N3.0 (5)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C1—H1A···O2i0.962.583.220 (8)124
C12—H12B···O2ii0.972.503.273 (5)136

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IS2351).

References

  • Enraf–Nonius (1989). CAD-4 Software Enraf–Nonius, Delft, The Netherlands.
  • Harms, K. & Wocadlo, S. (1995). XCAD4 University of Marburg, Germany.
  • Matsumoto, T., Hara, M. & Miyashita, K. (1996). PCT Int. Appl. WO 19 951 205.
  • Nagano, H., Yokota, T. & Katoh, Y. (1989). Eur. Pat. Appl. EP 89 108 963.
  • North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.
  • Petersen, U., Krebs, A. & Schenke, T. (1993). Eur. Pat. Appl. EP 92 122 058.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2003). J. Appl. Cryst.36, 7–13.

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography