1-Fluoronaphthalene → N,N-Dimethyl-3-((naphthalen-1-yl)oxy)-3-(thiophen-2-yl)propan-1-amine

Beteiligte Stoffe

Reaktionsschritte

In this example, 2-acetylthiophene is used as the starting material for reacting with formaldehyde and dimethylamine to form a Mannich product namely 3-dimethylamino-1-(2-thienyl)propan-1-one. A hydride reduction is performed on this propanone to form corresponding 3-dimethylamino-1-(2-thienyl)propan-1-ol. The resulting propanol is then reacted with fluoronaphthalene to form N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine. Subsequently, racemic Duloxetine® is obtained by demethylation of this propylamine. In this process, the yield of demethylation is very low, about 41%. In addition, Duloxetine® produced via this route is racemic. Resolution is therefore needed to obtain chiral Duloxetine which renders this process less competitive.

Herkunft & Nachweise