反应详情

6-tert-Butyl-3,4-dihydro-2H-isoquinolin-1-one (4 g, 19.67 mmol), Acetic acid 2,6-dibromo-benzyl ester (12.1 g, 2 eq), potassium phosphate tribasic (8.35 g, 2 eq) and copper iodide (787 mg, 0.2 eq) were taken up in dioxane (40 mL). Finally added N,N′-Dimethyl-cyclohexane-1,2-diamine (1.24 mL, 0.4 eq) and the resulting mixture was heated to reflux for 24 hours, after which time more copper iodide (394 mg, 0.1 eq) and N,N′-Dimethyl-cyclohexane-1,2-diamine (0.62 mL, 0.2 eq) were added. Stirred an additional 64 hours and then added more copper iodide (400 mg, 0.1 eq). Continued to stir at reflux for a total of 168 hours. Cooled to room temperature and then added ethylacetate (300 mL) and water (100 mL), partitioned and separated the layers. Washed with further water (2×100 mL) and then finally washed with brine (1×100 mL). The ethyl acetate layer was dried over magnesium sulfate, filtered and concentrated to give 4.45 g of crude product. Purification on a 240 g Analogix column afforded the title compound as a white foamy solid (516 mg) ((M+H)+=431) and recovered 6-tert-Butyl-3,4-dihydro-2H-isoquinolin-1-one (2.188 g).

1. temperatureto reflux for 24 hours
2. stirringContinued to stir
3. temperatureat reflux for a total of 168 hours
4. customadded ethylacetate (300 mL) and water (100 mL), partitioned
5. customseparated the layers
6. washWashed with further water (2×100 mL)
7. washfinally washed with brine (1×100 mL)
8. dry with materialThe ethyl acetate layer was dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customto give 4.45 g of crude product
12. customPurification on a 240 g Analogix column