反应详情

温度

50 °C

In a 2 L three-necked bottle flushed with N2, Mg (26.5 g, 1.1 mol) was warmed to 50° C., 1-bromo-3-chloro-5-fluorobenzene (157 g, 0.75 mol) solution in anhydrous THF (1 L) was added dropwise, then the mixture was stirred at r.t. for 2 hr. To a solution of (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (120 g, 0.441 mol) in anhydrous THF (1.1 L) at −78° C. under nitrogen was added dropwise the above Grignard reagent. The reaction mixture was allowed to warm to rt and stirred for 2 h. The mixture was quenched with saturated NH4Cl solution (500 mL) and extracted with EtOAc (3×400 mL). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo to give (R)-tert-butyl 3-(3-chloro-5-fluorobenzoyl)piperidine-1-carboxylate (163 g), which was used immediately without further purification.

1. temperatureto warm to rt
2. stirringstirred for 2 h
3. customThe mixture was quenched with saturated NH4Cl solution (500 mL)
4. extractionextracted with EtOAc (3×400 mL)
5. washThe combined organic layer was washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in vacuo