反应详情

A mixture of 5-chloro-2-iodoaniline (33.0 g, 0.13 mol) and 1-ethynyl-4-fluorobenzene (26.4 g, 0.22 mol) in diethylamine (400 mL) was degassed with bubbling nitrogen for 20 min., then tetrakis(triphenylphosphine)palladium(0) (2.0 g, 1.7 mmol) and copper (I) iodide (170 mg, 0.9 mmol) were added and the mixture was stirred at room temperature for 12 h. The solvent was evaporated under reduced pressure, water was added and the mixture was extracted with ethyl acetate. The combined organic fractions were washed with water (2×), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in dimethylformamide (250 mL), calcium carbonate (13 g, 0.13 mol) and copper (I) iodide (12.4 g, 0.07 mol) were added and the mixture was stirred at 120° C. for 22 h. The mixture was cooled, filtered and the solvent was evaporated under reduced pressure. Water was added and the mixture was extracted with ethyl acetate. The combined organic fractions were washed with water (2×) and brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was triturated with ether/hexane and the solid was collected and dried in vacuo to give the title compound (25.4 g, 85%). 1H NMR (360 MHz, CDCl3) δ 7.59 (2H, m), 7.49 (1H, d, J 8.5 Hz), 7.44 (1H, s), 7.24-6.99 (3H, m), and 6.69 (1H, d, J 1.8 Hz).

1. customwas degassed with bubbling nitrogen for 20 min.
2. customThe solvent was evaporated under reduced pressure, water
3. additionwas added
4. extractionthe mixture was extracted with ethyl acetate
5. washThe combined organic fractions were washed with water (2×)
6. dry with materialdried (MgSO4)
7. customthe solvent was evaporated under reduced pressure
8. dissolutionThe residue was dissolved in dimethylformamide (250 mL)
9. stirringthe mixture was stirred at 120° C. for 22 h
10. temperatureThe mixture was cooled
11. filtrationfiltered
12. customthe solvent was evaporated under reduced pressure
13. additionWater was added
14. extractionthe mixture was extracted with ethyl acetate
15. washThe combined organic fractions were washed with water (2×) and brine
16. dry with materialdried (MgSO4)
17. customthe solvent was evaporated under reduced pressure
18. customThe residue was triturated with ether/hexane
19. customthe solid was collected
20. customdried in vacuo