反应详情

温度

70 °C

A solution containing the product from Example 3G (2.0 g, 8.69 mmol) in a mixture of benzene (40 mL) and ethanol (40 mL) was treated with 4-quinolinecarboxaldehyde (1.4 g, 8.91 mmol), heated at 70° C. for 2 hours, cooled to 25° C., treated with sodium borohydride (1.0 g, 26.75 mmol), stirred at 25° C. for 16 hours, quenched with sodium bicarbonate solution and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. A solution of the residue (8.69 mmol) in 1,2-dichloroethane (300 mL) was treated with bis(4-nitrophenyl) carbonate (3.0 g, 9.86 mmol), heated at 70° C. for 16 hours, and partitioned between ethyl acetate and saturated NaHCO3. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. A solution of the residue (8.69 mmol) in dichloromethane (40 mL) was treated with trifluoracetic acid (40 mL), stirred at 25° C. for 1 hour and concentrated. The residue was chromatographed on silica gel eluting with 0-5% methanol in dichloromethane. A second purification using reversed phase chromatography on a C18 column, eluting with 5-100% acetonitrile in water (0.1% TFA) afforded the title compound (1.91 g, 48% yield).

1. temperaturecooled to 25° C.
2. customquenched with sodium bicarbonate solution
3. custompartitioned between ethyl acetate and water
4. washThe organic phase was washed with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. temperatureheated at 70° C. for 16 hours
9. custompartitioned between ethyl acetate and saturated NaHCO3
10. washThe organic phase was washed with brine
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated
14. stirringstirred at 25° C. for 1 hour
15. concentrationconcentrated
16. customThe residue was chromatographed on silica gel eluting with 0-5% methanol in dichloromethane
17. customA second purification
18. washeluting with 5-100% acetonitrile in water (0.1% TFA)