反应详情

温度

-75 °C

To a stirred solution of 1-chloro-2-fluoro-benzene (13.0 g, 0.1 mol) in THF (250 mL) at −75° C. was added dropwise 2.5 M BuLi in hexane (40 mL, 0.1 mol) over 45 min. After additional stirring for 30 min at −75° C., a solution of (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)-piperidine-1-carboxylate (21.76 g, 0.08 mol) in THF (100 mL) was added dropwise over 30 min. The mixture was allowed to warm from −70° C. to 0° C. The mixture was quenched with satd aq NH4Cl, extracted with EtOAc (3×) and the combined organic layers were dried over Na2SO4. Solvent removal and flash column chromatography, eluting with 5% EtOAc/PE afforded (R)-tert-butyl 3-(3-chloro-2-fluorobenzoyl)piperidine-1-carboxylate (19.2 g, 70%). 1H NMR (400 MHz, CDCl3): 1.45 (s, 9H), 1.63 (m, 2H), 1.76 (m, 1H), 2.06 (m, 1H), 2.87 (m, 1H), 3.15 (m, 1H), 3.25 (m, 1H), 3.9 (m, 1H), 4.2 (m, 1H), 7.18 (m, 1H), 7.60 (m, 2H). MS (E/Z): 342 (M+H+).

1. temperatureto warm from −70° C. to 0° C
2. customThe mixture was quenched with satd aq NH4Cl
3. extractionextracted with EtOAc (3×)
4. dry with materialthe combined organic layers were dried over Na2SO4
5. customSolvent removal and flash column chromatography
6. washeluting with 5% EtOAc/PE