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.

中文翻译：

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用（S）-扁桃酸拆分3-（甲基氨基）-1-（2-噻吩基）丙-1-醇（度洛西汀的新关键中间体）

研究了外消旋3-（甲基氨基）-1-（2-噻吩基）丙烷-1-醇3（度洛西汀1的新关键中间体）的拆分。条件进行了用于工业规模的分辨率优化3通过使用（小号） -扁桃酸4作为拆分试剂和含有2倍摩尔量的水作为溶剂的2-丁醇。胺释放后，将（S）-3 ·（S）-4 ·H ₂ O非对映异构体盐结晶，得到具有> 99.9％ee的纯（S）-3。释放的（-）- 3的绝对构型确定为（S）通过X射线晶体学。