Indomethacin methyl ester

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, England, and Pfizer Institute for Pharmaceutical Materials Science, Institute of Chemical and Engineering Sciences, Ayer Rajah Crescent, Block 28, Unit 02-08, Singapore 139959, and Pfizer Institute for Pharmaceutical Materials Science, and Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, England


Comment
As part of an investigation into the crystallization of pharmaceutical compounds, the crystal structures of indomethacin derivatives are of interest. Numerous studies have been reported on various crystal structures of the drug indomethacin (-form: Kistenmacher & Marsh, 1972;-form: Chen et al., 2002;t-butanol and methanol solvates: Joshi et al., 1998). In contrast, the structure of its methyl ester, (I), has not been reported to date. We report here its crystal structure and describe the intermolecular interactions involved.
The asymmetric unit of (I) comprises one molecule (Fig. 1). Although the crystal structure of the indomethacin methyl ester differs signi®cantly from that of the parent carboxylic acid, it bears some similarity to the structure of another indomethacin derivative, iodoindomethacin (Loll et al., 1996) In the absence of the carboxylic acid group of indomethacin, no strong OÐHÁ Á ÁO hydrogen bonding can be expected in the crystal structure of the methyl ester. Instead, CÐHÁ Á ÁO hydrogen bonds form a three-dimensional supramolecular network, as shown in Fig. 2. Hydrogen-bond distances and angles are provided in Table 1.

Crystal data
All H atoms were placed geometrically and treated using a riding model. The U iso values for methyl H atoms were ®xed at 1.5U eq of the carrier atom. For all other H atoms, U iso (H) = 1.2U eq (carrier atom). The CÐH distances of methyl groups were ®xed at 0.98 A Ê ; all other CÐH distances were ®xed at 0.95 A Ê .

Figure 1
Molecular unit showing displacement ellipsoids at the 50% probability level.

Figure 2
Projection on to (010) Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.