(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

Cai, X.; Zhou, X.; Zheng, Z.; Zhong, W.; Li, S.

doi:10.1107/S1600536810041164

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 (C-C) = 0.004 Å
Disorder in solvent or counterion
R = 0.032
wR = 0.079
Data-to-parameter ratio = 6.7
Details

(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

Xu Cai,^a Xinbo Zhou,^a ^* Zhibing Zheng,^a Wu Zhong ^a and Song Li ^a

^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-HO 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); Doshan & Perez (2006). For the bioactivity and synthesis of S-MNTX, see: Wagoner et al. (2006).

Experimental

Crystal data

C₂₁H₂₆NO₄⁺·C₂F₃O₂^-·CH₄O
M_r = 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 radiation
= 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) T_min = 0.976, T_max = 0.983
16033 measured reflections
2336 independent reflections
2261 reflections with I > 2(I)
R_int = 0.030

Refinement

R[F² > 2(F²)] = 0.032
wR(F²) = 0.079
S = 1.07
2336 reflections
349 parameters
66 restraints
H-atom parameters constrained
_max = 0.22 e Å^-3
_min = -0.19 e Å^-3

Table 1
Hydrogen-bond geometry (Å, °)

D-HA	D-H	HA	DA	D-HA
O1-H1O5ⁱ	0.84	1.79	2.622 (2)	170
O4-H4O7ⁱⁱ	0.84	1.86	2.685 (2)	169
O7-H7AO6ⁱⁱ	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); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); 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.
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.
Wagoner, H., Sanghvi, S. P., Boyd, T. A., Verbicky, C. & Andruski, S. (2006). WO Patent WO2006127898.

organic compounds