K. Sakai, R. Sakurai, A. Yuzawa
Jun 20, 2003
Citations
1
Influential Citations
23
Citations
Journal
Tetrahedron-asymmetry
Abstract
Abstract The resolution of racemic 3-(methylamino)-1-(2-thienyl)propan-1-ol 3, a new key intermediate for duloxetine 1, was studied. The conditions were optimized for an industrial-scale resolution of 3 by using (S)-mandelic acid 4 as a resolving agent and 2-butanol containing 2 equimolar amounts of water as a solvent. The (S)-3·(S)-4·H2O diastereomeric salt was crystallized to give pure (S)-3 with >99.9% e.e. after liberation of the amine. The absolute configuration of liberated (−)-3 was determined as (S) by X-ray crystallography.