反应详情

温度

0 °C

Add isopropylmagnesium chloride (2.0 M in THF, 235 mL, 470 mmol) over 15 minutes to a solution of 1-isopropylsulfonyl-2-amino-6-iodobenzimidazole (42.9 g, 118 mmol) in tetrahydrofuran (850 mL) at −70° C. under a nitrogen atmosphere. Stir for 1 hour at 0° C. and then add a solution of N-[methyl] N-[methoxy] 2-(tert-butyldimethylsilyl)oxy-2-(phenyl)acetamide (90.0 g, 294 mmol) (Tius, et al., Tetrahedron, 56, 3339-3351-(2000)) in tetrahydrofuran (150 mL) via cannula. Stir the resulting slurry at 0-5° C. for 1 hour and then at room temperature for 1.5 hours. Cool the mixture to 10° C. and then add saturated aqueous ammonium chloride. Stir the mixture 15 minutes and separate the layers. Extract the aqueous layer with ethyl acetate (400 mL), dry the combined organic layers over sodium sulfate, and concentrate under reduced pressure. Purify the residue by silica gel chromatography, eluting with 1-10% acetonitrile in dichloromethane containing 0.5% triethylamine to provide a 50% yield of the title compound as a white solid. MS(ES+): m/z=488.1 (M+H)+

1. stirringStir the resulting slurry at 0-5° C. for 1 hour
2. waitat room temperature for 1.5 hours
3. temperatureCool the mixture to 10° C.
4. stirringStir the mixture 15 minutes
5. customseparate the layers
6. extractionExtract the aqueous layer with ethyl acetate (400 mL)
7. dry with materialdry the combined organic layers over sodium sulfate
8. concentrationconcentrate under reduced pressure
9. customPurify the residue by silica gel chromatography
10. washeluting with 1-10% acetonitrile in dichloromethane containing 0.5% triethylamine