反应详情

温度

120 °C

The mixture of racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(5-fluoro-2-methylphenyl)-2,3-dihydro-1′-(3-chloro-propyl)-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane (0.24 g, 0.36 mmol) prepared in example 60a and morpholine (10 mL) was heated at 120° C. for 1 h. The mixture was concentrated to dryness. The resulting residue was added dichloromethane (20 mL) and then trifluoroacetic acid (20 mL). The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and saturated NaHCO3 solution. The organic layer was separated and concentrated. The residue was redissolved in methanol (10 mL). To the resulting solution was added N,N′-diisopropylethylamine (2 mL, 11.0 mmol) and the crude was heated at 100° C. for 1 h. The reaction mixture was concentrated and the residue was purified by chromatography (MeOH:EtOAc=1:9) to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(5-fluoro-2-methylphenyl)-1′-(3-morpholin-4-yl-propyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (Yield 0.08 g, 37.9%).

1. concentrationThe mixture was concentrated to dryness
2. additionThe resulting residue was added dichloromethane (20 mL)
3. concentrationThe reaction mixture was concentrated
4. customthe residue was partitioned between ethyl acetate and saturated NaHCO3 solution
5. customThe organic layer was separated
6. concentrationconcentrated
7. dissolutionThe residue was redissolved in methanol (10 mL)
8. temperaturethe crude was heated at 100° C. for 1 h
9. concentrationThe reaction mixture was concentrated
10. customthe residue was purified by chromatography (MeOH:EtOAc=1:9)