反应详情

温度

80 °C

6-Bromo-2-(4-methoxy-benzyl)-3,4-dihydro-2H-isoquinolin-1-one (5 g, 14.4 mmol), SPHOS (361 mg, 0.06 eq), cesium carbonate (5.65 g, 1.2 eq) and palladium acetate (130 mg, 0.04 eq) were placed in an open sealed tube and taken up in dioxane (58 mL). Argon was bubbled through the solution for about 15 minutes and then isobutyraldehyde (2.9 mL, 2 eq) was added and the mixture was capped and stired at 80° C. overnight. The next day the reaction still was not complete, so additional palladium acetate (65 mg) and SPHOS (181 mg) and isobutyraldehyde (1.5 mL) were added and the reaction was stirred at 80° C. for another 24 hours. At this point the reaction still was not complete so additional palladium acetate (30 mg) and SPHOS (90 mg) were added and the reaction was stirred at 100° C. for another 24 hours. After 3 days, there was no starting material remaining and the reaction was cooled to room temperature. Added ethyl acetate (300 ml) and water 100 mL) and partitioned and separated the layers. The ethyl acetate layer was washed with brine (100 mL) and dried over magnesium sulfate, filtered and concentrated to give the crude product. Purification on silica gel eluting with 20% ethyl acetate in hexanes afforded the title compound as a thick colorless oil (428 mg). MS (ESI) 338.0 (M+H)+.

1. customArgon was bubbled through the solution for about 15 minutes
2. customthe mixture was capped
3. customThe next day the reaction
4. customAt this point the reaction
5. additionwere added
6. stirringthe reaction was stirred at 100° C. for another 24 hours
7. waitAfter 3 days
8. temperaturethe reaction was cooled to room temperature
9. customAdded ethyl acetate (300 ml) and water 100 mL) and partitioned
10. customseparated the layers
11. washThe ethyl acetate layer was washed with brine (100 mL)
12. dry with materialdried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated
15. customto give the crude product
16. customPurification on silica gel eluting with 20% ethyl acetate in hexanes