Studies On The Syntheses Of Duloxetine And Atomoxetine

The present stituation of depression and importance of fluoxetine and its analogues were reviewed briefly. Duloxetine and atomoxetine were summarized in detail. Duloxetine, a 5-hydroxytryptamine (5-HT) and norepinephrine (NE) reuptake inhibitor, has been approved by FDA for the treatment of severe depression and stress urinary incontinence. Atomoxetine, a NE reuptake inhibitor, is the first non-stimulating drug for the treatment of Attention Deficit /Hyperactivity Disorder (ADHD).On the basis of the investigation about the synthetic methods of duloxetine, an economical and reasonable synthetic route was studied. The target compound was obtained through five steps from 2-acetylthiophene. Additionally, two different methods were tested, one was to react acetophenone with methylamine hydrochloride directly to avoid the process of N-demethylation, the other was using Williamson synthetic method to synthesize an intermediate, N.N-dimethyl -3-(l-naphthalenyloxy)-3-(2-thienyl)propanamine. The optically active intermediate, (S)-(-)-3-dimethylamino-l-(2-thienyl)-l-propanol, was obtained by chiral resolution, and (S)-(+)-duloxetine was also obtained with the total yield of 13.2% and the optical purity of 74.9%.The synthetic method of atomoxetine involved in six steps, including the...