反应详情

A mixture of tert-butyl piperazine-1-carboxylate (3.94 g, 21.6 mmol), 2-(4-bromo-3-chlorophenoxy)tetrahydropyran (5.61 g, 19.2 mol), palladium acetate (86.4 mg, 0.39 mmol), BINAP (172 mg, 0.58 mmol) and sodium tert-butoxide (2.4 g, 25.0 mmol) in toluene (40 ml) was refluxed under a nitrogen atmosphere for 2 hours. Ethyl acetate and water were added to the reaction mixture, which was stirred for a while. The insoluble substances were removed by filtration through Celite, and the filtrate was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=20/1) to afford tert-butyl 4-[2-chloro-4-(tetrahydropyran-2-yloxy)phenyl]piperazine-1-carboxylate (4.72 g, yield 62%) as a yellow oil.

1. temperaturewas refluxed under a nitrogen atmosphere for 2 hours
2. customThe insoluble substances were removed by filtration through Celite
3. extractionthe filtrate was extracted with ethyl acetate
4. washThe extract was washed with brine
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationThe filtrate was concentrated under reduced pressure
8. customthe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=20/1)