supplementary materials


kj2148 scheme

Acta Cryst. (2010). E66, o2660    [ doi:10.1107/S1600536810038249 ]

[(3R,4S)-4-(4-Fluorophenyl)-1-methylpiperidin-3-yl]methyl 4-methylbenzenesulfonate

J. Qi, H. Chen and C. Zhang

Abstract top

In the title compound, C20H24FNO3S, the piperidine ring adopts a chair conformation. The dihedral angle between the aromatic rings is 47.01 (17)°.

Comment top

The title compound is a useful intermediate in preparing paroxetine [(3S,4R)-4-(4-fluorophenyl)-3-(3,4-methylenedioxyphenoxymethyl)- piperidine]. Paroxetine is a well-known selective serotonin reuptake inhibitor (SSRI) antidepressant, used world wide in therapeutics (Segura et al., 2003). In view of the above, ((3R,4S)-4-(4-fluorophenyl)-1-methylpiperidin-3-yl)methyl 4-methylbenzenesulfonate was synthesized and its crystal structure is reported here. A perspective view of the structure with the atomic numbering scheme is shown in Fig. 1. The dihedral angle between the two benzene rings is 47.01 (17)°. The piperidine ring adopts a chair conformation. The piperidine ring contains three planes (C2/C4/C5/C6, C3/C4/N1/C6, C2/C3/C5/N1), the first one of which is more planar than the other two.

Related literature top

For general background to the design and synthesis of vinyl sulfonate derivatives, see: Curzons et al. (2003), Segura et al. (2003). For related structures, see: Wang & Kanagawa (1997).

Experimental top

To a stirred solution of trans-(-)-paroxo (10 g) in dichloromethane (50 ml) triethylamine (7 ml) was added. The mixture was cooled to 268 K. Toluenesulfonyl chloride (12 g) was slowly added and stirred for l h at 268 K. Methanesulfonic acid (4 ml) was then added gradually and the mixture was concentrated at about 323 K at atmospheric pressure. The residue was taken up in toluene, water was added and this was stirred for 30 minutes. The top toluene layer was separated. The pH of the aqueous layer was then adjusted to 9.0 with a saturated NaHCO3 solution. The product was filtered, washed with water and dried to yield the title compound (13 g) as a white to off-white solid (m.p. 380-381 K).

Refinement top

All H atoms were placed in calculated positions, with C—H distances in the range 0.93-0.98 and included in the final cycles of refinement in the riding-model approximation, with Uiso(H) = 1.2Ueq(C) or Uiso(H) = 1.5Ueq(C).

Computing details top

Data collection: PROCESS-AUTO (Rigaku, 2006); cell refinement: PROCESS-AUTO (Rigaku, 2006); data reduction: CrystalStructure (Rigaku/MSC, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound showing atom labels and 40% probability displacement ellipsoids.
[(3R,4S)-4-(4-Fluorophenyl)-1-methylpiperidin-3-yl]methyl 4-methylbenzenesulfonate top
Crystal data top
C20H24FNO3SF(000) = 400
Mr = 377.46Dx = 1.268 Mg m3
Monoclinic, P21Melting point: 380 K
Hall symbol: P 2ybMo Kα radiation, λ = 0.71073 Å
a = 9.1590 (4) ÅCell parameters from 7787 reflections
b = 10.0764 (5) Åθ = 3.0–27.4°
c = 10.7644 (6) ŵ = 0.19 mm1
β = 95.718 (1)°T = 296 K
V = 988.50 (9) Å3Chunk, yellow
Z = 20.32 × 0.26 × 0.20 mm
Data collection top
Rigaku R-AXIS RAPID
diffractometer
4457 independent reflections
Radiation source: rolling anode3114 reflections with I > 2σ(I)
graphiteRint = 0.021
Detector resolution: 10.00 pixels mm-1θmax = 27.4°, θmin = 3.0°
ω scansh = 1111
Absorption correction: multi-scan
(ABSCOR; Higashi, 1995)
k = 1313
Tmin = 0.931, Tmax = 0.963l = 1313
9742 measured reflections
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.031 w = 1/[σ2(Fo2) + (0.0395P)2 + 0.063P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.084(Δ/σ)max < 0.001
S = 1.00Δρmax = 0.17 e Å3
4457 reflectionsΔρmin = 0.14 e Å3
238 parametersExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.0052 (13)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983), 2086 Friedel pairs
Secondary atom site location: difference Fourier mapFlack parameter: 0.05 (6)
Crystal data top
C20H24FNO3SV = 988.50 (9) Å3
Mr = 377.46Z = 2
Monoclinic, P21Mo Kα radiation
a = 9.1590 (4) ŵ = 0.19 mm1
b = 10.0764 (5) ÅT = 296 K
c = 10.7644 (6) Å0.32 × 0.26 × 0.20 mm
β = 95.718 (1)°
Data collection top
Rigaku R-AXIS RAPID
diffractometer
4457 independent reflections
Absorption correction: multi-scan
(ABSCOR; Higashi, 1995)
3114 reflections with I > 2σ(I)
Tmin = 0.931, Tmax = 0.963Rint = 0.021
9742 measured reflectionsθmax = 27.4°
Refinement top
R[F2 > 2σ(F2)] = 0.031H-atom parameters constrained
wR(F2) = 0.084Δρmax = 0.17 e Å3
S = 1.00Δρmin = 0.14 e Å3
4457 reflectionsAbsolute structure: Flack (1983), 2086 Friedel pairs
238 parametersFlack parameter: 0.05 (6)
1 restraint
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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
xyzUiso*/Ueq
S10.34071 (5)0.65560 (6)0.19254 (4)0.05870 (14)
O10.37947 (12)0.66249 (15)0.33871 (9)0.0550 (3)
C140.51158 (17)0.6533 (2)0.13267 (13)0.0496 (4)
O20.2721 (2)0.52973 (18)0.17277 (14)0.0832 (5)
C20.4586 (2)0.77398 (17)0.53214 (15)0.0481 (4)
H20.48440.86190.56650.058*
O30.26443 (18)0.77282 (18)0.15090 (14)0.0788 (5)
N10.3547 (2)0.71908 (16)0.72847 (16)0.0659 (5)
C30.5921 (2)0.68346 (16)0.56744 (16)0.0533 (5)
H30.57030.59650.52920.064*
C70.7277 (2)0.73680 (18)0.51511 (18)0.0568 (5)
C40.6116 (2)0.6639 (3)0.70958 (16)0.0684 (5)
H4A0.68550.59630.73030.082*
H4B0.64630.74600.74920.082*
C10.4245 (2)0.79152 (17)0.39340 (16)0.0507 (4)
H1A0.34620.85580.37640.061*
H1B0.51050.82380.35710.061*
C150.5673 (2)0.7700 (2)0.08678 (18)0.0595 (5)
H150.51520.84910.08880.071*
C60.3242 (2)0.7278 (2)0.59338 (18)0.0615 (5)
H6A0.24410.78950.57290.074*
H6B0.29370.64140.56040.074*
C50.4712 (3)0.62325 (19)0.75996 (19)0.0737 (7)
H5A0.44090.53730.72600.088*
H5B0.48780.61480.85000.088*
C80.7843 (2)0.6761 (3)0.41456 (18)0.0696 (6)
H80.74240.59750.38280.083*
C190.5895 (3)0.5365 (2)0.12864 (18)0.0630 (5)
H190.55290.45830.15950.076*
C90.9024 (3)0.7304 (3)0.3602 (2)0.0862 (7)
H90.93990.68870.29310.103*
C170.7790 (2)0.6507 (4)0.03166 (18)0.0795 (6)
C180.7223 (3)0.5368 (3)0.0783 (2)0.0792 (7)
H180.77480.45800.07590.095*
C200.9241 (3)0.6477 (6)0.0255 (3)0.1361 (12)
H20A0.91070.60470.10540.204*
H20B0.99530.59980.02850.204*
H20C0.95790.73690.03570.204*
F11.07463 (15)0.9031 (2)0.35259 (18)0.1293 (7)
C130.2204 (3)0.6809 (4)0.7843 (2)0.1021 (10)
H13A0.19100.59340.75670.153*
H13B0.14350.74280.75900.153*
H13C0.23920.68150.87370.153*
C120.7948 (2)0.8534 (2)0.5606 (2)0.0732 (6)
H120.76030.89540.62880.088*
C100.9617 (2)0.8460 (3)0.4074 (3)0.0858 (7)
C160.7006 (3)0.7662 (3)0.0384 (2)0.0751 (7)
H160.73890.84440.00920.090*
C110.9115 (3)0.9079 (3)0.5067 (3)0.0885 (7)
H110.95510.98590.53790.106*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0645 (3)0.0783 (3)0.0327 (2)0.0102 (3)0.00190 (16)0.0008 (3)
O10.0736 (7)0.0586 (6)0.0328 (5)0.0118 (8)0.0056 (5)0.0006 (7)
C140.0649 (9)0.0540 (9)0.0294 (7)0.0033 (11)0.0024 (6)0.0024 (9)
O20.0960 (12)0.1015 (12)0.0521 (9)0.0489 (10)0.0078 (8)0.0117 (8)
C20.0602 (10)0.0463 (9)0.0372 (9)0.0004 (8)0.0026 (7)0.0028 (7)
O30.0729 (10)0.1132 (13)0.0492 (9)0.0227 (9)0.0005 (7)0.0127 (9)
N10.0924 (13)0.0687 (10)0.0391 (9)0.0094 (9)0.0187 (8)0.0068 (7)
C30.0747 (11)0.0445 (11)0.0392 (9)0.0079 (9)0.0017 (8)0.0071 (7)
C70.0597 (11)0.0611 (11)0.0475 (11)0.0165 (9)0.0053 (9)0.0066 (9)
C40.0977 (13)0.0628 (10)0.0419 (9)0.0124 (14)0.0073 (9)0.0007 (11)
C10.0588 (10)0.0501 (10)0.0429 (10)0.0019 (8)0.0036 (8)0.0031 (7)
C150.0787 (14)0.0583 (11)0.0409 (10)0.0056 (10)0.0027 (9)0.0054 (9)
C60.0715 (13)0.0689 (11)0.0452 (11)0.0076 (10)0.0106 (9)0.0042 (8)
C50.1250 (19)0.0585 (15)0.0376 (10)0.0056 (12)0.0081 (11)0.0020 (8)
C80.0716 (12)0.0842 (15)0.0506 (11)0.0210 (13)0.0051 (9)0.0139 (12)
C190.0824 (15)0.0587 (12)0.0467 (12)0.0019 (11)0.0004 (10)0.0012 (9)
C90.0689 (14)0.130 (2)0.0600 (15)0.0322 (14)0.0061 (11)0.0080 (13)
C170.0626 (11)0.1280 (19)0.0472 (11)0.0052 (18)0.0019 (8)0.0036 (16)
C180.0810 (17)0.0940 (17)0.0603 (14)0.0232 (14)0.0049 (12)0.0148 (13)
C200.0691 (14)0.253 (4)0.0883 (19)0.003 (3)0.0194 (13)0.009 (3)
F10.0667 (8)0.1822 (18)0.1440 (16)0.0034 (10)0.0364 (9)0.0170 (13)
C130.122 (2)0.131 (3)0.0591 (14)0.040 (2)0.0382 (13)0.0086 (15)
C120.0656 (12)0.0774 (14)0.0771 (15)0.0049 (11)0.0098 (11)0.0234 (11)
C100.0482 (12)0.118 (2)0.0909 (19)0.0140 (13)0.0073 (12)0.0047 (16)
C160.0785 (16)0.0988 (18)0.0482 (13)0.0271 (14)0.0079 (11)0.0101 (12)
C110.0601 (13)0.0933 (17)0.112 (2)0.0020 (12)0.0077 (13)0.0169 (15)
Geometric parameters (Å, °) top
S1—O31.4219 (18)C6—H6A0.9700
S1—O21.4220 (17)C6—H6B0.9700
S1—O11.5796 (10)C5—H5A0.9700
S1—C141.7510 (16)C5—H5B0.9700
O1—C11.469 (2)C8—C91.392 (3)
C14—C191.379 (3)C8—H80.9300
C14—C151.392 (3)C19—C181.380 (4)
C2—C11.505 (2)C19—H190.9300
C2—C61.527 (3)C9—C101.362 (4)
C2—C31.542 (2)C9—H90.9300
C2—H20.9800C17—C161.374 (4)
N1—C51.454 (3)C17—C181.375 (4)
N1—C61.456 (2)C17—C201.519 (3)
N1—C131.474 (3)C18—H180.9300
C3—C71.513 (3)C20—H20A0.9600
C3—C41.535 (2)C20—H20B0.9600
C3—H30.9800C20—H20C0.9600
C7—C81.387 (3)F1—C101.368 (3)
C7—C121.392 (3)C13—H13A0.9600
C4—C51.501 (3)C13—H13B0.9600
C4—H4A0.9700C13—H13C0.9600
C4—H4B0.9700C12—C111.380 (3)
C1—H1A0.9700C12—H120.9300
C1—H1B0.9700C10—C111.356 (4)
C15—C161.375 (3)C16—H160.9300
C15—H150.9300C11—H110.9300
O3—S1—O2119.85 (9)C2—C6—H6B109.3
O3—S1—O1109.40 (9)H6A—C6—H6B108.0
O2—S1—O1103.91 (9)N1—C5—C4111.70 (17)
O3—S1—C14108.92 (10)N1—C5—H5A109.3
O2—S1—C14109.32 (12)C4—C5—H5A109.3
O1—S1—C14104.29 (6)N1—C5—H5B109.3
C1—O1—S1117.67 (11)C4—C5—H5B109.3
C19—C14—C15120.08 (17)H5A—C5—H5B107.9
C19—C14—S1120.46 (16)C7—C8—C9121.4 (2)
C15—C14—S1119.45 (17)C7—C8—H8119.3
C1—C2—C6111.55 (15)C9—C8—H8119.3
C1—C2—C3113.27 (14)C14—C19—C18119.3 (2)
C6—C2—C3111.54 (15)C14—C19—H19120.4
C1—C2—H2106.7C18—C19—H19120.4
C6—C2—H2106.7C10—C9—C8118.5 (2)
C3—C2—H2106.7C10—C9—H9120.8
C5—N1—C6109.66 (15)C8—C9—H9120.8
C5—N1—C13110.76 (19)C16—C17—C18117.99 (19)
C6—N1—C13109.76 (18)C16—C17—C20121.4 (3)
C7—C3—C4113.49 (15)C18—C17—C20120.6 (4)
C7—C3—C2110.99 (14)C17—C18—C19121.7 (2)
C4—C3—C2109.40 (15)C17—C18—H18119.2
C7—C3—H3107.6C19—C18—H18119.2
C4—C3—H3107.6C17—C20—H20A109.5
C2—C3—H3107.6C17—C20—H20B109.5
C8—C7—C12117.4 (2)H20A—C20—H20B109.5
C8—C7—C3121.21 (18)C17—C20—H20C109.5
C12—C7—C3121.27 (18)H20A—C20—H20C109.5
C5—C4—C3112.10 (16)H20B—C20—H20C109.5
C5—C4—H4A109.2N1—C13—H13A109.5
C3—C4—H4A109.2N1—C13—H13B109.5
C5—C4—H4B109.2H13A—C13—H13B109.5
C3—C4—H4B109.2N1—C13—H13C109.5
H4A—C4—H4B107.9H13A—C13—H13C109.5
O1—C1—C2108.42 (13)H13B—C13—H13C109.5
O1—C1—H1A110.0C11—C12—C7121.4 (2)
C2—C1—H1A110.0C11—C12—H12119.3
O1—C1—H1B110.0C7—C12—H12119.3
C2—C1—H1B110.0C11—C10—C9122.2 (2)
H1A—C1—H1B108.4C11—C10—F1118.5 (3)
C16—C15—C14118.8 (2)C9—C10—F1119.3 (3)
C16—C15—H15120.6C17—C16—C15122.2 (2)
C14—C15—H15120.6C17—C16—H16118.9
N1—C6—C2111.50 (16)C15—C16—H16118.9
N1—C6—H6A109.3C10—C11—C12119.1 (2)
C2—C6—H6A109.3C10—C11—H11120.4
N1—C6—H6B109.3C12—C11—H11120.4
O3—S1—O1—C138.54 (14)C13—N1—C6—C2177.1 (2)
O2—S1—O1—C1167.66 (14)C1—C2—C6—N1176.31 (15)
C14—S1—O1—C177.84 (14)C3—C2—C6—N155.9 (2)
O3—S1—C14—C19161.67 (15)C6—N1—C5—C461.7 (2)
O2—S1—C14—C1929.00 (16)C13—N1—C5—C4177.04 (18)
O1—S1—C14—C1981.61 (16)C3—C4—C5—N157.2 (2)
O3—S1—C14—C1517.09 (17)C12—C7—C8—C90.8 (3)
O2—S1—C14—C15149.76 (15)C3—C7—C8—C9175.15 (18)
O1—S1—C14—C1599.62 (15)C15—C14—C19—C180.3 (3)
C1—C2—C3—C757.92 (18)S1—C14—C19—C18178.51 (16)
C6—C2—C3—C7175.24 (14)C7—C8—C9—C100.4 (3)
C1—C2—C3—C4176.09 (16)C16—C17—C18—C191.1 (3)
C6—C2—C3—C449.2 (2)C20—C17—C18—C19178.8 (2)
C4—C3—C7—C8129.5 (2)C14—C19—C18—C170.2 (3)
C2—C3—C7—C8106.83 (19)C8—C7—C12—C111.1 (3)
C4—C3—C7—C1254.7 (2)C3—C7—C12—C11174.8 (2)
C2—C3—C7—C1268.9 (2)C8—C9—C10—C111.3 (4)
C7—C3—C4—C5174.59 (17)C8—C9—C10—F1177.8 (2)
C2—C3—C4—C550.0 (2)C18—C17—C16—C151.7 (3)
S1—O1—C1—C2178.87 (11)C20—C17—C16—C15178.3 (2)
C6—C2—C1—O161.63 (18)C14—C15—C16—C171.3 (3)
C3—C2—C1—O165.21 (18)C9—C10—C11—C121.1 (4)
C19—C14—C15—C160.3 (3)F1—C10—C11—C12178.1 (2)
S1—C14—C15—C16179.04 (15)C7—C12—C11—C100.2 (4)
C5—N1—C6—C261.0 (2)
Acknowledgements top

Mr Jian-ming Gu of the X-ray crystallography facility of Zhejiang University is acknowledged for his assistance with the crystal structure analysis.

references
References top

Curzons, A. D. (2003). US Patent No. 20030187269

Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.

Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838.

Flack, H. D. (1983). Acta Cryst. A39, 876–881.

Higashi, T. (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan.

Rigaku (2006). PROCESS-AUTO. Rigaku Corporation, Tokyo, Japan.

Rigaku/MSC (2007). CrystalStructure. Rigaku/MSC, The Woodlands, Texas, USA.

Segura, M., Roura, L., De La Torre, R. & Joglar, J. (2003). Bioorg. Chem. 31, 248–258.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Wang, S. & Kanagawa, Y. (1997). Eur. Patent No. 0810225