Water → Duloxetine

Participants

Reaction Conditions

Reaction Steps

Sodium hydroxide (19 g) and water (25 mL) were added to a solution of (S)-N-Methyl-[3-(naphthalen-1-yloxy)-3-thiophen-2-yl-propyl]-carbamic acid phenyl ester (64.8 g) dissolved in DMSO (250 mL). The mixture was heated at 115° C. for 6 hours, cooled to ambient temperature, and water (200 mL) was added. The mixture was then extracted with toluene (2×200 mL) and the organic layers were combined. The organic layers were then washed with brine (100 mL), dried over sodium sulfate, filtered and concentrated. The resulting residue was then dissolved in methanol (500 mL), combined with activated carbon (2 g), and heated at reflux for 1 hour. After cooling, the mixture was filtered through Celite® (20 g), the filter cake was washed with methanol (50 mL), and the solution was concentrated to yield duloxetine base as an oil (37.07 g, Yield: 92% yield, Chiral HPLC: 90% ee).

Provenance & Evidence