反应详情

To a suspension of NaH (5.64 g, 0.141 mol) in the mixed solvent of DMF (70 mL) and THF (70 mL) at −25° C. was added dropwise a solution of (R)-tert-butyl 3-((R)-(5-chloro-2-methylphenyl)(hydroxy)methyl)piperidine-1-carboxylate (16 g, 47 mmol) in anhydrous THF (100 mL), the reaction mixture was stirred for 1 hr at rt. A solution of ethyl bromoacetate (15.6 g, 94 mmol) in anhydrous THF (70 mL) was added dropwise to the above mixture at −10-−5° C. After addition, the reaction mixture was stirred for 2-3 hr at rt. The reaction was quenched with saturated NH4Cl solution (100 mL) and EtOAc (500 mL) was added. The organic layer was washed with water (5×50 mL) and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography to afford (R)-tert-butyl 3-((R)-(5-chloro-2-methylphenyl)(2-ethoxy-2-oxoethoxy)methyl)piperidine-1-carboxylate (8 g, 18.8 mmol).

1. additionAfter addition
2. stirringthe reaction mixture was stirred for 2-3 hr at rt
3. customThe reaction was quenched with saturated NH4Cl solution (100 mL) and EtOAc (500 mL)
4. additionwas added
5. washThe organic layer was washed with water (5×50 mL) and brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified by column chromatography