Ammonia → Trichlorourethan

Me-PRX (150 g) is dissolved in toluene (450 ml) at room temperature. The mixture is then heated to reflux. At reflux, 2,2,2-trichloroethyl-chloroformate (120 ml) is added dropwise for about 2.5 hours. After about 3 hours at reflux, the reaction mixture is cooled, and ammonia 20% (300 ml) and water (300 ml) is added. The organic phase is separated and washed with water (500 ml), followed by brine (500 ml). The organic phase is then separated, dried over MgSO4, filtered. Toluene is then removed under reduced pressure to give 280.2 g of the 2,2,2-trichloroethyl carbamate of paroxetine. The carbamate is then hydrolyzed according to procedures set forth, for example, in Examples 5-7 to give paroxetine base. Paroxetine base may then be converted into the desired polymorphic form of, e.g., the hydrochloride acid addition salt such as the hemihydrate, anhydrate or solvate form as disclosed herein.

1. temperatureThe mixture is then heated to reflux
2. temperatureAt reflux
3. temperatureAfter about 3 hours at reflux
4. temperaturethe reaction mixture is cooled
5. customThe organic phase is separated
6. washwashed with water (500 ml)
7. customThe organic phase is then separated
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. customToluene is then removed under reduced pressure

ORD record

ord-a66d5453327f4de29bb9cf87ccfc59b6

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06956121B2