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Acta Crystallogr Sect E Struct Rep Online. 2010 December 1; 66(Pt 12): o3168.
Published online 2010 November 13. doi:  10.1107/S1600536810046271
PMCID: PMC3011484

rac-2-[2-(4-Fluoro­phen­yl)-2-oxo-1-phenyl­eth­yl]-4-methyl-3-oxo-N-phenyl­penta­namide

Abstract

The title compound, C26H24FNO3, is a critical inter­mediate of a selective and competitive inhibitor of the enzyme 3-hy­droxy-3-methyl­glutaryl-coenzyme A (HMG–CoA) reductase. Inter­molecular N—H(...)O hydrogen bonding generates a chain along [give direction] that is the dominant inter­action in the crystal packing. Inter­molecular C—H(...)O inter­actions are also observed.

Related literature

For related structures, see: Baumann et al. (1992 [triangle]). For the title compound as an inter­mediate in the preparation of the HMG-CoA reductase inhibitor atorvastatin, see: Roth et al. (1991 [triangle]); Wang et al. (2007 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o3168-scheme1.jpg

Experimental

Crystal data

  • C26H24FNO3
  • M r = 417.46
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o3168-efi1.jpg
  • a = 14.1694 (14) Å
  • b = 9.8307 (9) Å
  • c = 16.6367 (16) Å
  • β = 99.651 (2)°
  • V = 2284.6 (4) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.08 mm−1
  • T = 173 K
  • 0.15 × 0.10 × 0.05 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2005 [triangle]) T min = 0.990, T max = 0.996
  • 10555 measured reflections
  • 3792 independent reflections
  • 2493 reflections with I > 2σ(I)
  • R int = 0.027

Refinement

  • R[F 2 > 2σ(F 2)] = 0.067
  • wR(F 2) = 0.227
  • S = 1.06
  • 3792 reflections
  • 275 parameters
  • 1 restraint
  • H-atom parameters constrained
  • Δρmax = 0.78 e Å−3
  • Δρmin = −0.68 e Å−3

Data collection: SMART (Bruker, 2005 [triangle]); cell refinement: SAINT (Bruker, 2005 [triangle]); data reduction: SAINT; 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: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810046271/kp2271sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810046271/kp2271Isup2.hkl

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

Acknowledgments

The authors are grateful to the Sciences Foundation of the Shandong Provincial Education Department (No. J06D61) as well as the Doctoral Science Foundation of Zaozhuang University.

supplementary crystallographic information

Comment

The title compound, C26H24FNO3(I),(Fig. 1) is of value as an pharmaceutical intermediate, particularly an intermediate of an HMG-CoA reductase inhibitor, atorvastatin (Roth et al., 1991; Wang et al., 2007). Though this compound reveals an opposite chirality at C8 and C9, up to now, the absolute configuration has not been reported so far, enantiomers separation or sterespecific synthesis of enantiomer of the title compound. A racemic mixture is always directly used to prepare HMG-CoA reductase inhibitor. Using N-ethyl thiazolium bromide as the catalyst, reacting 4-fluorobenzaldehyde with benzylidine isobutyrylacetamide affords I, as a white solid (Baumann et al., 1992). Suitable crystals of I for single-crystal X-ray analysis were obtained by a vapor diffusion method. In the crystal structure intermolecular hydrogen bond N –H···O is a dominant interaction forming a chain (Table 1).

Experimental

2-Benzylidine isobutyrylacetamide (2.93 g, 10.0 mmol), N-ethyl thiazolium bromide (0.290 g, 1.50 mmol), 4-fluorobenzaldehyde (1.36 g, 11.0 mmol), and triethylamine (8.08 g, 8.00 mmol) were mixed and heated to 338 K. The reaction mixture was stirred for 24 h maintaining the temperature at 338 K. After 2-propanol (5 ml) and water (5 ml) were added, a white precipitate was formed. The precipitate was filtered, washed with 2-propanol, and dried to afford the title compound (2.09 g, 50.2%) as a white solid. Colourless crystals were obtained by vapor diffusion of pentane into an acetone solution over a period of 5 d. 1H NMR (500 MHz, CD3CN, 22 °C): δ 8.48 (1 H, s), 8.10 (2 H, m), 7.37 (2 H, m), 7.25 (6 H, m), 7.18 (3 H, m), 7.07 (1 H, m), 5.43 (1 H, d, J = 13.5 Hz), 4.74 (1 H, d, J = 13.5 Hz), 2.96 (1 H, m), 1.23 (3 H, d, J = 8.5 Hz), 1.02 (3 H, d, J = 8.0 Hz). 13 C NMR (125 MHz, CD3CN, 22 °C): δ 209.1, 197.5, 167.5, 165.5, 138.7, 136.2, 133.4, 132.5, 129.9, 129.8, 129.7, 128.8, 125.5, 120.9, 116.6, 64.2, 53.6, 40.7, 19.3, 18.2. ESI-MS: 440.2 [M + Na]+.

Refinement

All H atoms were placed in calculated positions and refined as riding, with C—H = 0.95–1.00 Å, and N—H = 0.88 Å, and Uiso(H) = 1.2–1.5 Ueq(C,N).

Figures

Fig. 1.
The molecular structure with atom labels and 45% probability displacement ellipsoids for non-H atoms.
Fig. 2.
The packing diagram of molecular, viewed down the b axis, with the N—H···O interactions shown as dashed lines.

Crystal data

C26H24FNO3F(000) = 880
Mr = 417.46Dx = 1.214 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 2549 reflections
a = 14.1694 (14) Åθ = 2.4–21.8°
b = 9.8307 (9) ŵ = 0.08 mm1
c = 16.6367 (16) ÅT = 173 K
β = 99.651 (2)°Prism, colourless
V = 2284.6 (4) Å30.15 × 0.10 × 0.05 mm
Z = 4

Data collection

Bruker SMART CCD area-detector diffractometer3792 independent reflections
Radiation source: fine-focus sealed tube2493 reflections with I > 2σ(I)
graphiteRint = 0.027
[var phi] and ω scansθmax = 24.5°, θmin = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 2005)h = −16→15
Tmin = 0.990, Tmax = 0.996k = −11→11
10555 measured reflectionsl = −14→19

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.067Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.227H-atom parameters constrained
S = 1.06w = 1/[σ2(Fo2) + (0.1129P)2 + 1.1017P] where P = (Fo2 + 2Fc2)/3
3792 reflections(Δ/σ)max < 0.001
275 parametersΔρmax = 0.78 e Å3
1 restraintΔρmin = −0.68 e Å3

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
C10.0713 (3)0.2839 (5)0.9806 (3)0.0948 (13)
H1A0.03610.26911.02360.114*
C20.0430 (3)0.3814 (5)0.9239 (3)0.0996 (14)
H2A−0.01070.43680.92860.120*
C30.0911 (2)0.4006 (4)0.8599 (2)0.0769 (10)
H3A0.06980.46740.81960.092*
C40.1710 (2)0.3222 (3)0.85420 (17)0.0521 (7)
C50.2012 (3)0.2269 (3)0.9127 (2)0.0763 (10)
H5A0.25690.17450.91000.092*
C60.1503 (4)0.2071 (4)0.9758 (2)0.0958 (14)
H6A0.17050.13981.01590.115*
C70.2586 (2)0.2567 (3)0.74381 (17)0.0499 (7)
C80.2898 (2)0.3116 (3)0.66692 (17)0.0546 (7)
H8A0.27280.41030.66170.066*
C90.2357 (2)0.2362 (3)0.59207 (18)0.0617 (8)
H9A0.25630.13880.59480.074*
C100.1280 (3)0.2419 (4)0.5882 (2)0.0743 (10)
C110.0794 (4)0.3651 (5)0.5882 (3)0.1127 (15)
H11A0.11400.44820.59080.135*
C12−0.0191 (4)0.3675 (8)0.5845 (4)0.142 (2)
H12A−0.05110.45240.58450.170*
C13−0.0706 (5)0.2506 (10)0.5810 (4)0.146 (2)
H13A−0.13810.25310.57820.175*
C14−0.0231 (5)0.1283 (8)0.5815 (3)0.131 (2)
H14A−0.05800.04560.57930.158*
C150.0746 (3)0.1249 (5)0.5851 (2)0.0931 (12)
H15A0.10590.03940.58550.112*
C160.3973 (2)0.2978 (3)0.6729 (2)0.0695 (9)
C170.4603 (3)0.3732 (5)0.7404 (3)0.1074 (10)
H17A0.41830.42990.76970.129*
C180.5129 (5)0.2730 (6)0.8006 (4)0.168 (3)
H18A0.55330.32250.84470.253*
H18B0.55310.21420.77280.253*
H18C0.46650.21730.82340.253*
C190.5271 (3)0.4666 (5)0.7060 (3)0.1074 (10)
H19A0.56690.51580.75050.161*
H19B0.48980.53190.66900.161*
H19C0.56810.41330.67590.161*
C200.2594 (3)0.2989 (3)0.5144 (2)0.0752 (10)
C210.2747 (2)0.2140 (3)0.44349 (17)0.0595 (8)
C220.2713 (2)0.0741 (3)0.44226 (19)0.0632 (8)
H22A0.25920.02610.48900.076*
C230.2853 (3)0.0031 (4)0.3737 (2)0.0784 (10)
H23A0.2820−0.09340.37250.094*
C240.3038 (3)0.0743 (4)0.3080 (2)0.0821 (11)
C250.3089 (3)0.2124 (4)0.3068 (2)0.0882 (11)
H25A0.32210.25930.26000.106*
C260.2945 (3)0.2819 (4)0.3749 (2)0.0776 (10)
H26A0.29800.37840.37540.093*
N10.21798 (16)0.3485 (2)0.78690 (14)0.0535 (6)
H10.22070.43400.77190.066 (9)*
O10.26887 (16)0.13615 (19)0.76232 (13)0.0648 (6)
O20.2615 (3)0.4226 (3)0.50929 (17)0.1281 (13)
O30.4304 (2)0.2291 (3)0.62480 (19)0.1088 (11)
F10.3192 (2)0.0052 (3)0.24109 (15)0.1311 (11)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.107 (3)0.106 (3)0.087 (3)−0.021 (3)0.061 (3)−0.016 (3)
C20.066 (2)0.147 (4)0.092 (3)0.020 (2)0.032 (2)−0.018 (3)
C30.069 (2)0.094 (3)0.071 (2)0.0213 (19)0.0209 (17)−0.0039 (19)
C40.0572 (17)0.0468 (15)0.0567 (17)−0.0004 (13)0.0220 (13)−0.0059 (13)
C50.106 (3)0.0581 (19)0.075 (2)0.0208 (18)0.045 (2)0.0083 (17)
C60.160 (4)0.064 (2)0.080 (3)0.010 (2)0.066 (3)0.0072 (19)
C70.0563 (16)0.0431 (16)0.0535 (16)−0.0041 (12)0.0186 (13)−0.0047 (12)
C80.0694 (19)0.0447 (15)0.0550 (17)−0.0097 (13)0.0256 (14)−0.0043 (13)
C90.089 (2)0.0455 (16)0.0534 (17)−0.0118 (15)0.0210 (15)−0.0043 (13)
C100.086 (2)0.080 (2)0.0550 (19)−0.017 (2)0.0062 (16)0.0002 (16)
C110.095 (3)0.098 (3)0.139 (4)0.002 (3)0.001 (3)0.005 (3)
C120.087 (4)0.169 (6)0.163 (6)0.025 (4)0.003 (3)0.013 (4)
C130.090 (4)0.215 (8)0.125 (5)−0.029 (5)0.001 (3)0.002 (5)
C140.107 (4)0.173 (6)0.113 (4)−0.059 (4)0.015 (3)0.000 (4)
C150.103 (3)0.101 (3)0.077 (2)−0.038 (2)0.018 (2)−0.002 (2)
C160.077 (2)0.067 (2)0.073 (2)−0.0159 (17)0.0366 (18)−0.0126 (17)
C170.098 (2)0.116 (2)0.111 (2)−0.0421 (18)0.0240 (18)−0.0169 (19)
C180.165 (6)0.151 (6)0.163 (6)0.002 (4)−0.051 (5)0.006 (4)
C190.098 (2)0.116 (2)0.111 (2)−0.0421 (18)0.0240 (18)−0.0169 (19)
C200.117 (3)0.0525 (19)0.061 (2)−0.0195 (18)0.0282 (19)−0.0035 (15)
C210.070 (2)0.0604 (19)0.0477 (16)−0.0125 (15)0.0091 (14)−0.0014 (14)
C220.071 (2)0.061 (2)0.0578 (18)−0.0119 (15)0.0107 (15)−0.0049 (15)
C230.096 (3)0.068 (2)0.072 (2)−0.0158 (19)0.0166 (19)−0.0157 (18)
C240.097 (3)0.096 (3)0.055 (2)−0.012 (2)0.0169 (18)−0.025 (2)
C250.121 (3)0.095 (3)0.051 (2)−0.015 (2)0.0210 (19)−0.0007 (19)
C260.112 (3)0.068 (2)0.0532 (19)−0.0108 (19)0.0178 (18)0.0008 (16)
N10.0659 (15)0.0405 (13)0.0598 (14)0.0020 (11)0.0268 (12)0.0001 (11)
O10.0940 (16)0.0417 (12)0.0663 (13)0.0069 (10)0.0355 (11)0.0004 (9)
O20.261 (4)0.0547 (16)0.0844 (19)−0.0303 (19)0.076 (2)−0.0051 (13)
O30.0924 (19)0.129 (2)0.121 (2)−0.0246 (17)0.0629 (18)−0.0555 (19)
F10.195 (3)0.128 (2)0.0799 (16)−0.0225 (19)0.0503 (17)−0.0418 (15)

Geometric parameters (Å, °)

C1—C21.357 (6)C14—C151.376 (7)
C1—C61.363 (6)C14—H14A0.9500
C1—H1A0.9500C15—H15A0.9500
C2—C31.370 (5)C16—O31.201 (4)
C2—H2A0.9500C16—C171.507 (6)
C3—C41.387 (4)C17—C191.499 (6)
C3—H3A0.9500C17—C181.509 (7)
C4—C51.366 (4)C17—H17A1.0000
C4—N11.419 (3)C18—H18A0.9800
C5—C61.383 (5)C18—H18B0.9800
C5—H5A0.9500C18—H18C0.9800
C6—H6A0.9500C19—H19A0.9800
C7—O11.227 (3)C19—H19B0.9800
C7—N11.341 (3)C19—H19C0.9800
C7—C81.521 (4)C20—O21.220 (4)
C8—C161.516 (5)C20—C211.490 (4)
C8—C91.539 (4)C21—C221.375 (4)
C8—H8A1.0000C21—C261.390 (4)
C9—C101.517 (5)C22—C231.379 (4)
C9—C201.520 (4)C22—H22A0.9500
C9—H9A1.0000C23—C241.361 (5)
C10—C151.372 (5)C23—H23A0.9500
C10—C111.394 (6)C24—F11.352 (4)
C11—C121.387 (7)C24—C251.360 (6)
C11—H11A0.9500C25—C261.368 (5)
C12—C131.357 (8)C25—H25A0.9500
C12—H12A0.9500C26—H26A0.9500
C13—C141.377 (8)N1—H10.8800
C13—H13A0.9500
C2—C1—C6120.0 (3)C10—C15—C14121.7 (5)
C2—C1—H1A120.0C10—C15—H15A119.2
C6—C1—H1A120.0C14—C15—H15A119.2
C1—C2—C3120.7 (4)O3—C16—C17121.6 (4)
C1—C2—H2A119.7O3—C16—C8120.4 (3)
C3—C2—H2A119.7C17—C16—C8118.0 (3)
C2—C3—C4119.7 (4)C19—C17—C16110.4 (4)
C2—C3—H3A120.2C19—C17—C18112.4 (5)
C4—C3—H3A120.2C16—C17—C18109.8 (4)
C5—C4—C3119.6 (3)C19—C17—H17A108.0
C5—C4—N1123.7 (3)C16—C17—H17A108.0
C3—C4—N1116.7 (3)C18—C17—H17A108.0
C4—C5—C6119.8 (3)C17—C18—H18A109.5
C4—C5—H5A120.1C17—C18—H18B109.5
C6—C5—H5A120.1H18A—C18—H18B109.5
C1—C6—C5120.3 (4)C17—C18—H18C109.5
C1—C6—H6A119.9H18A—C18—H18C109.5
C5—C6—H6A119.9H18B—C18—H18C109.5
O1—C7—N1124.0 (2)C17—C19—H19A109.5
O1—C7—C8121.0 (2)C17—C19—H19B109.5
N1—C7—C8115.0 (2)H19A—C19—H19B109.5
C16—C8—C7110.1 (3)C17—C19—H19C109.5
C16—C8—C9111.7 (2)H19A—C19—H19C109.5
C7—C8—C9109.5 (2)H19B—C19—H19C109.5
C16—C8—H8A108.5O2—C20—C21119.7 (3)
C7—C8—H8A108.5O2—C20—C9118.3 (3)
C9—C8—H8A108.5C21—C20—C9121.9 (3)
C10—C9—C20108.3 (3)C22—C21—C26118.6 (3)
C10—C9—C8112.2 (3)C22—C21—C20124.2 (3)
C20—C9—C8110.0 (2)C26—C21—C20117.2 (3)
C10—C9—H9A108.8C21—C22—C23120.6 (3)
C20—C9—H9A108.8C21—C22—H22A119.7
C8—C9—H9A108.8C23—C22—H22A119.7
C15—C10—C11117.3 (4)C24—C23—C22118.5 (3)
C15—C10—C9121.0 (4)C24—C23—H23A120.7
C11—C10—C9121.7 (3)C22—C23—H23A120.7
C12—C11—C10120.5 (5)F1—C24—C25118.3 (3)
C12—C11—H11A119.7F1—C24—C23118.8 (4)
C10—C11—H11A119.7C25—C24—C23122.9 (3)
C13—C12—C11121.2 (6)C24—C25—C26118.1 (3)
C13—C12—H12A119.4C24—C25—H25A121.0
C11—C12—H12A119.4C26—C25—H25A121.0
C12—C13—C14118.7 (6)C25—C26—C21121.3 (3)
C12—C13—H13A120.7C25—C26—H26A119.4
C14—C13—H13A120.7C21—C26—H26A119.4
C15—C14—C13120.6 (6)C7—N1—C4126.8 (2)
C15—C14—H14A119.7C7—N1—H1116.6
C13—C14—H14A119.7C4—N1—H1116.6

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.882.102.959 (2)178 (4)
C1—H1A···O3ii0.952.433.371 (5)169
C5—H5A···O10.952.522.963 (4)109
C26—H26A···O20.952.412.735 (4)100

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: KP2271).

References

  • Baumann, K. L., Butler, D. E., Deering, C. F., Mennen, K. E., Millar, A., Nanninga, T. N., Palmer, C. W. & Roth, B. D. (1992). Tetrahedron Lett.33, 2283–2284.
  • Bruker (2005). SMART, SAINT and SADABS Bruker AXS Inc., Madison, Wisconsin, USA.
  • Roth, B. D., Blankley, C. J., Chucholowski, A. W., Ferguson, E., Hoefle, M. L., Ortwine, D. F., Newton, R. S., Sekerke, C. S., Sliskovic, D. R., Stratton, C. D. & Wolson, M. (1991). J. Med. Chem.34, 357–366. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Wang, J., Shen, J., Wang, L., Wang, W., Cai, Z. & Du, Z. (2007). Chin. J. Synth. Chem.15, 519–527.

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