| Fluoxetine hydrochloride is one of the second-generation antidepressants in clinical, which is the selective serotonin reuptake inhibitors (SSRIs) and affects neurotransmitter receptors. It is used for the treatment of various types of depression and for anxiety disorders and atypical depression.Many methods for the synthesis of fluoxetine hydrochloride were reported in documents. In the present paper, the advantages and disadvantages in those methods were reviewed in detail and a suitable procedure for the industrial production was designed and investigated, which has the features of fewer steps, higher yield, low cost. In this process acetophenone reacted with methylamine hydrochloride and para-formaldehyde via Mannich reaction (yields 71.0%), followed by the reduction reaction through potassium borohydride in methanol (yields 84.8%) and then reacted with 4-chlorobenzo- trifluoride in the system of DMSO/KOH by etherification reaction, finally fluoxetine hydrochloride was formed (yields 68.1%), the total yield was 41%. Meanwhile HPLC method for determining the purity was established, and the purity of fluoxetine hydrochloride reached the requirement of the United States and the British Pharmacopoeia (purity 99.42%).In addition, atomoxetine hydrochloride which is the drug for treatment of attention deficit hyperactivity disorder, was synthesized using the similar method for the preparation of fluoxetine hydrochloride. The process of synthesizing atomoxetine hydrochloride was optimized and the total yield of 31% was achieved. |
