OPTICAL RESOLUTION OF RACEMIC ALBUTEROL BY DIASTEREOMERIC SALTS FORMED WITH DI-TOLUOYL-D-TARTARIC ACID

FERRAYOLI CARLOS; PALACIO MARCELA; BRESINA M.FERNANDA; PALACIOS SARA

Chicago, Illinois, USA

Simposio; 11th International Symposium on Chiral Driscrimination; 1999

Internatioanl Symposia on chirals Driscrimination

Approximately 20% of all available drugs are sold as mixtures of stereoisomers. In view of the pronounced differences in activity between enantiomers, and the regulatory position that argued that racemic drugs should not longer be used because one enantiomer is active and the other is inactive, many drugs have to be resolved to quiral ones. This is the case of Albuterol (1), a drug widely used for treatment of asthma, being the R-isomer the most active enantiomer. Most of the method to obtain R-albuterol deal with the resolution of an early synthetic intermediate. In our case, we found an easy method of resolution of the racemate. As Albuterol is a secondary amine, different chiral acids were screened for resolution, and it was found that the di-p-tpluoyl-D-tarataric acid (2) achieve good results. When an equivalent of 1 was mixed with an equivalent of 2, in reflux methanol, 60% of the dissolved mass crystallized after cooling, with an enantiomeric enrichment of R/S=70/30. In the next crystallization in methanol, a purity of R/S=99.5/0.5 was reached. The obtained salt was dissolved in water an after acidification with sulfuric acid and extraction with ether (3 times), the water was evaporated resulting in approximately 40% yield of R-albuterol sulfate, with an optical purity of 99,5%. Optimization of the process and conditions for the racemization of the residual S-isomers, will be discussed.