Cesium carbonate → cis-3,5-Dimethyl-1-[2-(methyloxy)-5-nitrophenyl]piperazine

Cesium carbonate (9.77 g, 30 mmol), palladium (II) acetate (448 mg, 2 mmol) and rac-2,2′-bis(diphenylphosphino)-1,1′-binapthyl (1.87 g, 3 mmol) were stirred under an inert atmosphere in tetrahydrofuran (40 ml) for 30 minutes. 2-Bromo-4-nitroanisole (4.64 g, 20 mmol) and cis-2,6-dimethylpiperazine (6.85 g, 60 mmol) in tetrahydrofuran (20 ml) was added and the mixture heated at reflux for 24 hours. After cooling to room temperature the reaction mixture was diluted with ethyl acetate and extracted with 2N hydrochloric acid (×3). The aqueous extract was stirred with ethyl acetate and activated charcoal, filtered through celite. The aqueous component of the filtrate was separated and the pH of the solution was adjusted to pH 7 with 50% potassium hydroxide solution and the solution evaporated in vacuo to a small volume. The residue was basified to pH 10 with 50% potassium hydroxide solution and extracted with dichloromethane (×3). The combined organic extracts were washed with saturated brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford the title product (D1). MS (ES+) m/e 266 [M+H]+.

1. temperaturethe mixture heated
2. temperatureat reflux for 24 hours
3. extractionextracted with 2N hydrochloric acid (×3)
4. extractionThe aqueous extract
5. filtrationfiltered through celite
6. customThe aqueous component of the filtrate was separated
7. customthe solution evaporated in vacuo to a small volume
8. extractionextracted with dichloromethane (×3)
9. washThe combined organic extracts were washed with saturated brine
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationconcentrated in vacuo

ORD-Eintrag

ord-6d92d0e683b643f7adf8a5f3a68a5fca

Quelldatensatz

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07381728B2