2-Bromo­beclometasone dipropionate

Kamal Aziz Ketuly; A Hamid A Hadi; Seik Weng Ng

doi:10.1107/S1600536809025987

. 2009 Jul 11;65(Pt 8):o1822. doi: 10.1107/S1600536809025987

2-Bromobeclometasone dipropionate

Kamal Aziz Ketuly ^a, A Hamid A Hadi ^a, Seik Weng Ng ^a,^*

PMCID: PMC2977202 PMID: 21583524

Abstract

In the crystal structure of 2-bromobeclometasone dipropionate [systematic name: (8S,9R,10S,11S,13S,14S,16S,17R)-2-bromo-9α-chloro-11-hydroxy-10,13,16-trimethyl-3-oxo-17-[2-(propionyloxy)acetyl]-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate], C₂₈H₃₆BrClO₇, the six-membered ring with the 1,4-diene-3-one composition is planar (r.m.s. deviations = 0.03 and 0.04 Å for the two independent molecules), whereas the remaining six-membered rings have chair conformations. Each of the independent molecules self-associates via O—H⋯O_propionate hydrogen bonding, generating a supramolecular chain running along the b axis. The crystal is twinned, with the monoclinic unit cell emulating an orthorhomic crystal system; the major twin component constitutes approximately 60%.

Related literature

For the NMR and crystal structure of the asthma drug beclometasone dipropionate monohydrate, see: Othman et al. (2008 ▶); Duax et al. (1981 ▶).

Experimental

Crystal data

C₂₈H₃₆BrClO₇
M _r = 599.93
Monoclinic,
a = 12.0999 (3) Å
b = 13.8673 (3) Å
c = 16.7971 (4) Å
β = 90.106 (1)°
V = 2818.4 (1) Å³
Z = 4
Mo Kα radiation
μ = 1.60 mm⁻¹
T = 140 K
0.22 × 0.11 × 0.02 mm

Data collection

Bruker SMART APEX diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.642, T _max = 0.746 (expected range = 0.834–0.969)
23151 measured reflections
12754 independent reflections
9841 reflections with I > 2σ(I)
R _int = 0.045

Refinement

R[F ² > 2σ(F ²)] = 0.046
wR(F ²) = 0.086
S = 0.94
12754 reflections
680 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.61 e Å⁻³
Δρ_min = −0.52 e Å⁻³
Absolute structure: Flack (1983 ▶), 6028 Friedel pairs
Flack parameter: 0.001 (7)

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: X-SEED (Barbour, 2001 ▶); software used to prepare material for publication: publCIF (Westrip, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809025987/tk2487sup1.cif

e-65-o1822-sup1.cif^{(42.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809025987/tk2487Isup2.hkl

e-65-o1822-Isup2.hkl^{(623.5KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O7ⁱ	0.82	2.11	2.817 (5)	145
O9—H9⋯O14ⁱⁱ	0.82	1.98	2.754 (5)	158

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

We thank the University of Malaya for supporting this study.

supplementary crystallographic information

Experimental

The synthesis of the compound is described in a 1988 study commissioned by the Glaxo company (now called Glaxo Smith Kline), External Report No. WAP/88/007.

The brominated compound was isolated from the mother liquor of the first crystallization of beclomethasone dipropionate (10 g). This was dissolved in hexane:ethyl acetate (8:1 v/v) and eluted by flash-column silica gel chromatography with nitrogen at 20 psi. This procedure was repeated for other batches to accumulate more material. The combined fractions were further fractioniated on fresh silica gel. One of the fractions (162 mg) yielded crystals that were recrystallized from hexane:ethyl acetate (3:1 v/v) (47 mg); 490–491 K. Elemental analysis: Calc. for C₂₈H₃₆BrClO₇: C 56.19, H 6.02, Br 13.21, Cl, 5.85%. Found: C 56.03, H 6.12, Br 12.97, Cl, 5.76% . MS^+.599.