反应详情

1-(tert-Butoxycarbonyl)-4-piperidinemethanol (400 mg) was added to a mixture of 60% sodium hydride (90 mg) and DMF (11 mL) under ice-cooling in a nitrogen atmosphere, and the mixture was stirred for 10 minutes. A solution of 4-bromo-1-(bromomethyl)-2-(trifluoromethyl)benzene (550 mg) in DMF (2 mL) was added to the mixture under ice-cooling. After the reaction mixture was stirred for 30 minutes under ice-cooling, the temperature of the reaction mixture was raised to room temperature, and stirring was performed for 30 minutes. After a saturated aqueous ammonium chloride solution was added to the reaction mixture, extraction thereof was performed using an EtOAc-Hex mixed solvent (1:1), and the extract was washed with water and saturated brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hex:EtOAc=99:1 to 90:10), whereby tert-butyl 4-({[4-bromo-2-(trifluoromethyl)benzyl]oxy}methyl)piperidine-1-carboxylate (598 mg) was obtained as a pale yellow oil.

1. temperaturecooling in a nitrogen atmosphere
2. temperaturecooling
3. stirringAfter the reaction mixture was stirred for 30 minutes under ice-
4. temperaturecooling
5. stirringstirring
6. waitwas performed for 30 minutes
7. additionmixed solvent (1:1)
8. washthe extract was washed with water and saturated brine
9. dry with materialThe organic layer was dried over MgSO4
10. filtrationfiltered
11. concentrationthe filtrate was concentrated under reduced pressure
12. customThe residue was purified by silica gel column chromatography (Hex:EtOAc=99:1 to 90:10)