反应详情

To a solution of the compound prepared in Example 62 (2.35 g, 6.2 mmol) in N,N-dimethylformamide (50 mL) at 0° C. was added methyl 4-(2-bromoacetyl)phenylcarbamate (2.04 g, 7.49 mmol) followed by cesium carbonate (4.47 g, 13.7 mmol). The reaction was warmed to room temperature and stirred for 1.5 h whereupon the mixture was filtered through diatomaceous earth and the filter cake washed with dichloromethane. The filtrate was concentrated to afford crude product as a yellow solid. To a suspension of crude material in xylene (45 mL) in a glass pressure bottle was added ammonium acetate (2.88 g, 37.4 mmol). The reaction vessel was filled with nitrogen, sealed and heated at 140° C. for 1 h whereupon the mixture was cooled to room temperature, concentrated and partitioned between ethyl acetate (200 mL) and water (50 mL). The organic layer was washed with aqueous sodium bicarbonate solution and brine, dried and concentrated. Purification by flash chromatography (silica gel, 120 g, 40-60% ethyl acetate/dichloromethane then 3-5% methanol/dichloromethane) afforded the title compound (2.42 g, 71% for two steps) as a pale yellow solid.

1. filtrationwas filtered through diatomaceous earth
2. washthe filter cake washed with dichloromethane
3. concentrationThe filtrate was concentrated
4. customto afford crude product as a yellow solid
5. additionThe reaction vessel was filled with nitrogen
6. customsealed
7. temperatureheated at 140° C. for 1 h whereupon the mixture
8. temperaturewas cooled to room temperature
9. concentrationconcentrated
10. custompartitioned between ethyl acetate (200 mL) and water (50 mL)
11. washThe organic layer was washed with aqueous sodium bicarbonate solution and brine
12. customdried
13. concentrationconcentrated
14. customPurification by flash chromatography (silica gel, 120 g, 40-60% ethyl acetate/dichloromethane