R. Sakurai, A. Yuzawa, K. Sakai
Jul 11, 2008
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Journal
Tetrahedron-asymmetry
Abstract
Abstract The resolution of 3-aminopyrrolidine 1 , a versatile key intermediate for chiral pharmaceuticals, via diastereomeric salt formation was investigated. The resolution conditions were optimized focusing on an industrial-scale production to afford enantiopure ( R )- 1 , while ( S )-methoxy-2-phenylacetic acid 5 was found to be a suitable resolving agent. The less-soluble diastereomeric salt, 1:2 ( R )- 1 :( S )- 5 , was obtained with high resolution efficiency ( E ) (yield 44%, 98% de, E 86%) under the best resolution conditions; ( RS )- 1 /( S )- 5 /HCl molar ratio = 1.0/1.0/1.0 in water solvent in the presence of sodium chloride. The optimized resolution process was scaled up to a pilot-scale production using 50 kg of ( RS )- 1 dihydrochloride as a starting racemate, and the resolution efficiency successfully reproduced the laboratory results.