[Journal logo]

Volume 69 
Part 12 
Pages o1794-o1795  
December 2013  

Received 3 October 2013
Accepted 6 November 2013
Online 20 November 2013

Key indicators
Single-crystal X-ray study
T = 115 K
Mean [sigma](C-C) = 0.005 Å
R = 0.021
wR = 0.052
Data-to-parameter ratio = 18.6
Details
Open access

A triclinic polymorph of (-)-(S)-N-benzyl-2-[(R)-6-fluoro­chroman-2-yl]-2-hy­droxy­ethanaminium bromide

aInstitut de Chimie Moleculaire de l'Universite de Bourgogne - ICMUB, UMR CNRS 6302, Universite de Bourgogne, 9, Av. Alain Savary, 21078 Dijon CEDEX, France, and bCordenPharma-Synkem, 47 rue de Longvic, 21301 Chenove, France
Correspondence e-mail: Yoann.Rousselin@u-bourgogne.fr

The title salt, C18H21FNO2+·Br-, determined at 115 K, crystallizes in the triclinic space group P1. The previously reported polymorph occurs in the monoclinic space group P21 and has two independent mol­ecules in the asymmetric unit [Peeters et al. (1993[Peeters, O. M., Blaton, N. M. & De Ranter, C. J. (1993). Acta Cryst. C49, 2157-2160.]). Acta Cryst. C49, 2157-2160]. In the title molecule, the pyran rings adopt half-chair conformations. The absolute configuration is S for the hy­droxy-bearing C atom and R for the asymmetric C atom in the di­hydro­pyran unit. In the crystal, the components are linked by N-H...Br and O-H...Br hydrogen bonds, forming chains along the c-axis direction. The crystal studied was refined as an inversion twin.

Related literature

For the synthesis of the enanti­opure title product, see: Jas et al. (2011[Jas, G., Freifeld, I. & Kesseler, K. (2011). Patent WO 2011091968 (Corden PharmaChem GmbH).]). For studies of related isomers, see: Cini et al. (1990[Cini, M., Crotti, P. & Macchia, F. (1990). Tetrahedron Lett. 31, 4661-4664.]); Tuchalski et al. (2006[Tuchalski, G., Emmerling, F., Gröger, K., Hänsicke, A., Nagel, T. & Reck, G. (2006). J. Mol. Struct. 800, 28-44.], 2008[Tuchalski, G., Hänsicke, A., Reck, G. & Emmerling, F. (2008). Acta Cryst. E64, o54.]); Rousselin et al. (2012[Rousselin, Y., Bruel, A. & Clavel, A. (2012). Acta Cryst. E68, o3352.]). for the monoclinic polymorph, see: Peeters et al. (1993[Peeters, O. M., Blaton, N. M. & De Ranter, C. J. (1993). Acta Cryst. C49, 2157-2160.]). The title compound is a key inter­mediate in the synthesis of the beta blocker DL-nebivolol [systematic name: 1-(6-fluoro­chroman-2-yl)-{[2-(6-fluoro­chroman-2-yl)-2-hy­droxy-eth­yl]amino}­ethanol. For the pharmacological properties of nebivolol, see: Van Lommen et al. (1990[Van Lommen, G. R. E., de Bruyn, M. F. L. & Schroven, M. F. J. (1990). J. Pharm. Belg. 45, 355-360.]). For puckering parameters, see: Cremer & Pople (1975[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.]). For background to polymorphism, see: Bernstein (2002[Bernstein, J. (2002). In Polymorphism in Molecular Crystals. Oxford: Clarendon Press.]).

[Scheme 1]

Experimental

Crystal data
  • C18H21FNO2+·Br-

  • Mr = 382.27

  • Triclinic, P 1

  • a = 4.9248 (2) Å

  • b = 5.5117 (2) Å

  • c = 16.3894 (7) Å

  • [alpha] = 83.721 (2)°

  • [beta] = 89.038 (2)°

  • [gamma] = 86.765 (2)°

  • V = 441.48 (3) Å3

  • Z = 1

  • Mo K[alpha]1 radiation

  • [mu] = 2.35 mm-1

  • T = 115 K

  • 0.25 × 0.2 × 0.2 mm

Data collection
  • Nonius KappaCCD diffractometer with APEXII detector

  • Absorption correction: multi-scan (SADABS; Bruker, 2012[Bruker (2012). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.61, Tmax = 0.74

  • 10328 measured reflections

  • 3903 independent reflections

  • 3886 reflections with I > 2[sigma](I)

  • Rint = 0.020

Refinement
  • R[F2 > 2[sigma](F2)] = 0.021

  • wR(F2) = 0.052

  • S = 1.11

  • 3903 reflections

  • 210 parameters

  • 3 restraints

  • H-atom parameters constrained

  • [Delta][rho]max = 0.37 e Å-3

  • [Delta][rho]min = -0.18 e Å-3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]); refined as an inversion twin

  • Absolute structure parameter: 0.013 (7)

Table 1
Hydrogen-bond geometry (Å, °)

D-H...A D-H H...A D...A D-H...A
N1-H1A...Br1i 0.99 2.40 3.306 (2) 152
N1-H1B...Br1ii 0.99 2.30 3.258 (2) 162
O2-H2A...Br1i 0.84 2.47 3.2198 (19) 149
Symmetry codes: (i) x, y-1, z-1; (ii) x, y, z-1.

Data collection: APEX2 (Bruker, 2012[Bruker (2012). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2012[Bruker (2012). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]); software used to prepare material for publication: OLEX2.


Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: GW2140 ).


Acknowledgements

We thank Ms Marie-Jose Penouilh for the NMR spectra and for ESI mass spectra.

References

Bernstein, J. (2002). In Polymorphism in Molecular Crystals. Oxford: Clarendon Press.
Bruker (2012). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
Cini, M., Crotti, P. & Macchia, F. (1990). Tetrahedron Lett. 31, 4661-4664.
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.  [CrossRef] [ChemPort] [Web of Science]
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.  [Web of Science] [CrossRef] [ChemPort] [IUCr Journals]
Flack, H. D. (1983). Acta Cryst. A39, 876-881.  [CrossRef] [IUCr Journals]
Jas, G., Freifeld, I. & Kesseler, K. (2011). Patent WO 2011091968 (Corden PharmaChem GmbH).
Peeters, O. M., Blaton, N. M. & De Ranter, C. J. (1993). Acta Cryst. C49, 2157-2160.  [CSD] [CrossRef] [IUCr Journals]
Rousselin, Y., Bruel, A. & Clavel, A. (2012). Acta Cryst. E68, o3352.  [CSD] [CrossRef] [IUCr Journals]
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [ChemPort] [IUCr Journals]
Tuchalski, G., Emmerling, F., Gröger, K., Hänsicke, A., Nagel, T. & Reck, G. (2006). J. Mol. Struct. 800, 28-44.  [Web of Science] [CSD] [CrossRef] [ChemPort]
Tuchalski, G., Hänsicke, A., Reck, G. & Emmerling, F. (2008). Acta Cryst. E64, o54.  [CSD] [CrossRef] [IUCr Journals]
Van Lommen, G. R. E., de Bruyn, M. F. L. & Schroven, M. F. J. (1990). J. Pharm. Belg. 45, 355-360.  [PubMed] [ChemPort]


Acta Cryst (2013). E69, o1794-o1795   [ doi:10.1107/S1600536813030377 ]

This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.