Resolution of 3-(methylamino)-1-(2-thienyl) propan-1-ol, a new key intermediate for duloxetine, with (S)-mandelic acid

K Sakai, R Sakurai, A Yuzawa, Y Kobayashi…

文献索引：Sakai, Kenichi; Sakurai, Rumiko; Yuzawa, Atsushi; Kobayashi, Yuka; Saigo, Kazuhiko Tetrahedron Asymmetry, 2003 , vol. 14, # 12 p. 1631 - 1636

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被引用次数: 42

摘要

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% ee after liberation of the amine. The ...