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The Pharmaceutical Society of Korea (대한약학회)
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Preparative Method of R-(-)-Ibuprofen by Diastereomer Crystallization

  • Published : 2006.01.01
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Abstract

The economic and effective method for preparation of R-(-)-ibuprofen by diastereomer crystallization was developed. R-(-)-ibuprofen was resolved from racemic ibuprofen by forming R-(-)ibuprofen-R-(+)-$\alpha$-methylbenzylamine diastereomeric salt with R-(+)-$\alpha$-methylbenzylamine and crystallization. The purity of R-(-)-ibuprofen-R-(+)-$\alpha$-methylbenzylamine diastereomeric salt was tested and confirmed using HPLC and $^1H-NMR$ method. The pure diastereomeric salt collected from repeated recrystallization was further fractionated by liquid-liquid extraction to the pure enantiomer without racemization. R-(-)-ibuprofen was recovered producing overall yield of 2.4% with the purity more than 99.97%.

Keywords

References

  1. Abushoffa, A. M., Fillet, M., Servais, A. C., Hubert, P., and Crommen, J., Enhancement of selectivity and resolution in the enantioseparation of uncharged compounds using oppositelt chargeed cyclodextrin in cappilary electrophoresis. Electrophoresis, 24, 343-350 (2003) https://doi.org/10.1002/elps.200390044
  2. Bonato, P. S., Del Lama, M. P., and de Carvalho, R., Enantioselective determination of ibuprofen in plasma by highperformance liquid chromatography-electrospray mass spectrometry. J. Chromatgr. B. Analyt. Technol. Biomed .Life Sci., 796, 413-420 (2003) https://doi.org/10.1016/j.jchromb.2003.08.031
  3. Canaparo, R., Muntonim, E., Zaram, G. P., Della pepa, C., Berno, E., Costa, M., and Eandi, M., Determination of ibuprofen in Human plasma by high performance liquid chromatography: Validation and application in pharmacokinetic study. Biomed. Chromatogr., 14, 219-226 (2000) https://doi.org/10.1002/1099-0801(200006)14:4<219::AID-BMC969>3.0.CO;2-Z
  4. Ducret, A., Trani, M., Pepin, P., and Rorbert, Lorti., Chiral high performance liquide chromatography resolution of ibuprofen esters. J. Pharm. Biomed. Anal., 16, 1225-1231 (1997) https://doi.org/10.1016/S0731-7085(97)00212-4
  5. Johannsen, M., Separation of enantiomers of ibuprofen on chiral stationary phases by packed column supercritical fluid chromatography. J. Chromatogr. A, 937, 135-138 (2001) https://doi.org/10.1016/S0021-9673(01)01330-9
  6. Lana, E. Jane, Romas, J., Kazlauskas, and Quick, E., A fast Spectrophotometric Method to measure the enantioselectivity of Hydrolases. J. Org. Chem., 62, 4560-4561 (1997) https://doi.org/10.1021/jo9707803
  7. Makino, K., Yano, T., Maiguma, T., Teshima, D., Sendo, T., Itoh, Y., and Oishi, R., Arapid and simultaneous determination of several alnagesic anti-inflammatory agenr by cappilary zone electrophoresis. Ther. Drud. Monit., 25, 574-580(2003) https://doi.org/10.1097/00007691-200310000-00006
  8. Stephanie, E. Sen and Keith S. aniiker, $^{1}H$-NMR analysis of R/S Ibuprofen by the Formation of Diastereomeric Pair. J. Chem. Edu., 73-6, 569-572 (1996)
  9. Van Overbeke, A., Baeyens, W., Van den Bossche, W., and Dewaele, C., Enantiomeric separation of amide derivatives of some 2- arylpropionic acids by HPLC on a cellulose-based chiral stationary phase. J. Pharm. Biomed. Anal., 12, 911- 916 (1994) https://doi.org/10.1016/0731-7085(94)E0012-P
  10. Wei, W., Yu, X., u H., Simultaneous determination of several antalgic drugs based on their interactions with betacyclodextrin by cappilary zone electrophoresis. J. Chromatogr. Sci., 42, 155-160 (2004) https://doi.org/10.1093/chromsci/42.3.155