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Use of enantioselective liquid chromatography for preparation of pure atenolol enantiomers
Author(s) -
Mikuldaš Hrvoje,
Cepanec Ivica,
Šporec Anita,
Litvić Mladen,
Vinković Vladimir
Publication year - 2005
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.200401831
Subject(s) - atenolol , enantiomer , chemistry , diethylamine , enantioselective synthesis , chromatography , isopropyl , resolution (logic) , organic chemistry , catalysis , medicine , artificial intelligence , computer science , blood pressure , radiology
The study reported here shows a practicable preparation of pure atenolol enantiomers using enantioselective liquid chromatography. The successful separation of enantiomers of the final atenolol and the intermediate ester and the good peak shapes could not have been obtained without diethylamine as a component of the mobile phase. That makes difficult the recycling of the three‐component mobile phase, an unavoidable step in simulated moving bed chromatography separation technology. The only suitable methodology for preparation of atenolol enantiomers proved to be synthesis from its N ‐benzyl‐ N ‐isopropyl precursor and the chiral stationary phase Chiralpak AD was found to be very convenient for preparative separation of these enantiomers. The enantiomeric purities and recovery of separated enantiomers of this N ‐benzyl‐ N ‐isopropyl precursor were very high, allowing high enantiomeric purities of the final products, ee 's 99.3% for S‐ and 99.0% for R‐ atenolol. The chromatographic separation parameters, as well as solubility of racemate in the mobile phase, are good bases for the further examination of possible scale‐up resolution of compound 6 .