Water → Duloxetine

Temperature

115 °C

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).

1. temperaturecooled to ambient temperature
2. extractionThe mixture was then extracted with toluene (2×200 mL)
3. washThe organic layers were then washed with brine (100 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe resulting residue was then dissolved in methanol (500 mL)
8. temperatureheated
9. temperatureat reflux for 1 hour
10. temperatureAfter cooling
11. filtrationthe mixture was filtered through Celite® (20 g)
12. washthe filter cake was washed with methanol (50 mL)
13. concentrationthe solution was concentrated

ORD record

ord-b2621702ca5b433f9abec1afc78d3fb6

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158808B2