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Volume 66 
Part 11 
Page o2868  
November 2010  

Received 2 October 2010
Accepted 13 October 2010
Online 20 October 2010

Key indicators
Single-crystal X-ray study
T = 113 K
Mean [sigma](C-C) = 0.004 Å
Disorder in solvent or counterion
R = 0.032
wR = 0.079
Data-to-parameter ratio = 6.7
Details
Open access

(3S,4R,4aS,7aR,12bS)-3-Cyclopropylmethyl-4a,9-dihydroxy-3-methyl-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methano-1-benzofuro[3,2-e]isoquinolin-3-ium 2,2,2-trifluoroacetate methanol solvate

aBeijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China
Correspondence e-mail: hapwave@yahoo.cn

In the title compound, C21H26F3NO6+·CF3COO-·CH3OH or S-MNTX·CF3COO-·CH3OH (MNTX = methylnaltrexone), the conformation of the polycyclic backbone of the noroxymorphone skeleton can be simplified in terms of the angles between the least-squares planes of these rings. The dihedral angle between the cyclohexene and piperidine rings is 84.5 (6)°, while the dihedral angles between the planes of cyclohexane ring and the benzene, cyclohexene and piperidine rings, respectively, are 85.8 (6),80.0  (7) and 10.3 (7)°. In the crystal, molecules are linked by O-H...O hydrogen bonds. The trifluoroacetate F atoms are disordered in a 0.710 (14):0.710 (14) ratio. The absolute stereochemistry was inferred from the use of (4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one as one of the starting materials.

Related literature

For general background to methylnaltrexone (MNTX) bromide and R-MNTX, see: Crabtree (1984[Crabtree, B. L. (1984). Clin Pharm. 3, 273-280.]); Doshan & Perez (2006[Doshan, H. D. & Perez, J. (2006). WO Patent, WO 2006127899.]). For the bioactivity and synthesis of S-MNTX, see: Wagoner et al. (2006[Wagoner, H., Sanghvi, S. P., Boyd, T. A., Verbicky, C. & Andruski, S. (2006). WO Patent WO2006127898.]).

[Scheme 1]

Experimental

Crystal data
  • C21H26NO4+·C2F3O2-·CH4O

  • Mr = 501.49

  • Orthorhombic, P 21 21 21

  • a = 9.404 (2) Å

  • b = 12.526 (3) Å

  • c = 19.693 (5) Å

  • V = 2319.8 (10) Å3

  • Z = 4

  • Mo K[alpha] radiation

  • [mu] = 0.12 mm-1

  • T = 113 K

  • 0.20 × 0.18 × 0.14 mm

Data collection
  • Rigaku Saturn CCD area detector diffractometer

  • Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear. Rigaku/MSC,The Woodlands Texas, USA.]) Tmin = 0.976, Tmax = 0.983

  • 16033 measured reflections

  • 2336 independent reflections

  • 2261 reflections with I > 2[sigma](I)

  • Rint = 0.030

Refinement
  • R[F2 > 2[sigma](F2)] = 0.032

  • wR(F2) = 0.079

  • S = 1.07

  • 2336 reflections

  • 349 parameters

  • 66 restraints

  • H-atom parameters constrained

  • [Delta][rho]max = 0.22 e Å-3

  • [Delta][rho]min = -0.19 e Å-3

Table 1
Hydrogen-bond geometry (Å, °)

D-H...A D-H H...A D...A D-H...A
O1-H1...O5i 0.84 1.79 2.622 (2) 170
O4-H4...O7ii 0.84 1.86 2.685 (2) 169
O7-H7A...O6ii 0.84 1.88 2.698 (2) 166
Symmetry codes: (i) [-x+2, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (ii) [-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}].

Data collection: CrystalClear (Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear. Rigaku/MSC,The Woodlands Texas, USA.]); cell refinement: CrystalClear; data reduction: CrystalClear; 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: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: XCIF in SHELXTL.


Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HG2721 ).


Acknowledgements

This work was supported by the National Science Foundation of China and grant No. 2009ZX09501-005.

References

Crabtree, B. L. (1984). Clin Pharm. 3, 273-280.  [ChemPort] [PubMed]
Doshan, H. D. & Perez, J. (2006). WO Patent, WO 2006127899.
Rigaku/MSC (2005). CrystalClear. Rigaku/MSC,The Woodlands Texas, USA.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [details]
Wagoner, H., Sanghvi, S. P., Boyd, T. A., Verbicky, C. & Andruski, S. (2006). WO Patent WO2006127898.


Acta Cryst (2010). E66, o2868  [ doi:10.1107/S1600536810041164 ]

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