反应详情

温度

130 °C

To a solution of racemic 3-[1-aminomethyl-5-(tert-butyl-dimethyl-silanyloxy)-3,3-dimethyl-pentyl]-6-chloro-1,3-dihydro-indol-2-one (1.5 g, 3.5 mmol) in toluene (30 mL) was added 3-chloro-2-fluoro-benzaldehyde (Oakwood) (0.56 g, 3.5 mmol) and a catalytic amount of p-toluenesulfonic acid monohydrate (67 mg, 0.35 mmol). The reaction mixture was heated at 130° C. for 2 h. The mixture was cooled to room temperature, then partitioned between ethyl acetate and aqueous NaHCO3 solution. The organic layer was separated, and aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over MgSO4 and concentrated. The residue was purified by chromatography (50-100% EtOAc in hexanes) to give rac-(2′S,3′S,4′S)-4′-[4-(tert-butyl-dimethyl-silanyloxy)-2,2-dimethyl-butyl]-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-1H-spiro[indole-3,3′-pyrrolidin]-2-one as a white solid (0.12 g, 6%)

1. temperatureThe mixture was cooled to room temperature
2. custompartitioned between ethyl acetate and aqueous NaHCO3 solution
3. customThe organic layer was separated
4. extractionaqueous layer was extracted with ethyl acetate
5. dry with materialdried over MgSO4
6. concentrationconcentrated
7. customThe residue was purified by chromatography (50-100% EtOAc in hexanes)