反应详情

温度

97.5 °C

Add thiophene-2-carboxaldehyde (3.16 mL, 33.8 mmol) to a stirring mixture of 1-isopropylsulfonyl-2-amino-6-(α-((tert-butyldimethylsilyl)oxy)-α-(phenyl)acetyl)-benzimidazole (15.0 g, 30.8 mmol), copper(II) acetate (11.2 g, 61.5 mmol), and ammonium acetate (23.7 g, 308 mmol) in acetic acid (300 mL). Heat the mixture at 95-100° C. and stir vigorously for 2 hours. Cool the mixture to 15° C., pour into a mixture of 750 mL saturated aqueous ammonium chloride and 250 mL concentrated ammonium hydroxide. Adjust the mixture to pH 10 with ammonium hydroxide precooled to 5° C. and then add 4 L 4:1 ethyl acetate:methanol. Separate the layers and wash the organic layer with saturated aqueous ammonium chloride (500 mL), dry over magnesium sulfate and concentrate under reduced pressure. Subject the residue to silica gel chromatography eluting with dichloromethane containing from 15-50% acetonitrile and 0.5% triethylamine. Suspend the recovered material in ethanol (75 mL), warm to 55-60° C. for 30 minutes, cool to −10° C. for 30 minutes, filter, wash sequentially with cold ethanol followed by diethyl ether. Dry under reduced pressure to provide the title compound in 40% yield as a dark yellow powder. MS(ES+): m/z=464.1 (M+H)+

1. temperatureCool the mixture to 15° C.
2. customprecooled to 5° C.
3. customSeparate the layers
4. washwash the organic layer with saturated aqueous ammonium chloride (500 mL)
5. dry with materialdry over magnesium sulfate
6. concentrationconcentrate under reduced pressure
7. washeluting with dichloromethane containing from 15-50% acetonitrile and 0.5% triethylamine
8. temperaturewarm to 55-60° C. for 30 minutes
9. temperaturecool to −10° C. for 30 minutes
10. filtrationfilter
11. washwash sequentially with cold ethanol
12. customDry under reduced pressure