反应详情

温度

-78 °C

To a solution of 2-bromo-4-fluoro-1-methylbenzene (10.6 g, 0.056 mol) in anhydrous THF (150 mL) at −78° C. under nitrogen was added dropwise a solution of 2.5 M n-BuLi in hexane (22 mL, 0.056 mol). After stirring for 1 hr at −78° C., a solution of (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (10 g, 0.037 mol) in anhydrous THF (120 mL) was added dropwise. After addition, the reaction mixture was allowed to warn to rt and stirred for 2 hr. The mixture was quenched with saturated NH4Cl (100 mL) solution and extracted with EtOAc (3×80 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to provide crude (R)-tert-butyl 3-(5-fluoro-2-methylbenzoyl)piperidine-1-carboxylate (10.5 g, yield 88%), which was used in the next step without purification.

1. additionAfter addition
2. customto warn to rt
3. stirringstirred for 2 hr
4. customThe mixture was quenched with saturated NH4Cl (100 mL) solution
5. extractionextracted with EtOAc (3×80 mL)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo