反应详情

温度

45 °C

Solid 1-tert-butoxycarbonyl-4-(5-fluoro-2-oxo-1-benzimidazolinyl)piperidine (9.7 g, 28.9 mmol.) was dissolved in anhydrous DMF (72 mL) under an inert atmosphere and cesium carbonate (10.6 g, 32.5 mmol.) was added followed by excess 2,2,2-trifluoroethyl iodide (14.3 mL, 145 mmol.). This reaction mixture was gently warmed at 40-50° C. for an extended period (1-2 days), periodically adding additional 2,2,2-trifluoroethyl iodide (4 mL, 4 mmol in four portions) to drive the alkylation to completion. The cooled reaction mixture was diluted with EtOAc and washed with aq. NaHCO3 and water (3×). The organic layer was dried (Na2SO4) and filtered through a pad of charcoal and the solvent then evaporated. The solid residue was triturated with Et2O and collected to give 1-tert-butoxycarbonyl-4-(5-fluoro-3-(2,2,2-tri-fluoroethyl)-2-oxo-1-benzimidazolinyl)piperidine as a nearly pure white solid. This material was crystallized from CH2C2 to remove a slightly less polar impurity affording the product, mp: 172-173° C.

1. additionwas added
2. customThe cooled reaction mixture
3. washwashed with aq. NaHCO3 and water (3×)
4. dry with materialThe organic layer was dried (Na2SO4)
5. filtrationfiltered through a pad of charcoal
6. customthe solvent then evaporated
7. customThe solid residue was triturated with Et2O
8. customcollected