反应详情

温度

80 °C

To a solution of 7-bromo-1,4,4,6-tetramethyl-3,4-dihydro- 1H-quinoline-2-one (example 1d) (0.96 g, 3.40 mmol) in dioxane (2 mL) were added under argon, triethylamine 1.9 mL, 13.61 mmol), palladium acetate (38 mg, 0.17 mmol), 2-(dicyclohexylphosphino) biphenyl (238 mg, 0.68 mmol) and pinacolborane (1M in THF, 10.2 mL, 10.2 mmol). The mixture was stirred at 80° C. for 1 hr 45 min, then cooled to room temperature. Water (1.5 mL), barium hydroxide octahydrate (3.22 g, 10.20 mmol) and 2-Fluoro-3-iodo-4-methoxy benzaldehyde dissolved in dioxane (7 mL) were successively added and the mixture heated at 100° C. for 13 hrs. The mixture was cooled to room temperature and filtered over celite. Brine was added and the aqueous layer was extracted with dichloromethane. The organic extract was washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified on silica gel (20% to 30% ethyl acetate in hexane) to give 0.63 g of 2-Fluoro-4-methoxy-3-(1,4,4,6-tetramethyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-yl)-benzaldehyde (52%). 1H NMR (300 MHz; CDCl3): 1.33 (s, 3 H), 1.35 (s, 3 H), 2.09 (s, 3 H), 2.54 (s, 2 H), 3.35 (s, 3 H), 3.87 (s, 3 H), 6.79 (s, 1 H), 6.92 (d, J=8.7 Hz, 1 H), 7.21 (s, 1 H), 7.94 (t, J=8.7 Hz, 1 H), 10.25 (s, 1 H).

1. temperaturecooled to room temperature
2. additionwere successively added
3. temperaturethe mixture heated at 100° C. for 13 hrs
4. temperatureThe mixture was cooled to room temperature
5. filtrationfiltered over celite
6. additionBrine was added
7. extractionthe aqueous layer was extracted with dichloromethane
8. extractionThe organic extract
9. washwas washed successively with water and brine
10. dry with materialdried over anhydrous magnesium sulfate
11. filtrationfiltered
12. customevaporated
13. customThe residue was purified on silica gel (20% to 30% ethyl acetate in hexane)