反应详情

温度

110 °C

In a 350-mL pressure-tube was added 4-bromo-2,6-difluorophenol (23.82 g, 0.11 mol), triethylamine (55 mL, 0.39 mol), ethyl acrylate (34.27 g, 0.34 mol), DMF (50 mL), palladium (II) acetate (1.29 g, 5.75 mmol), and tri-o-tolyphosphine (2.34 g, 7.6 mmol) under N2. The mixture was sealed in the glass tube and was stirred at 110° C. overnight (21 hours). The reaction was cooled to room temperature and EtOAc (150 mL) was added. The mixture was stirred for 30 minutes, filtered through celite and rinsed with EtOAc (100 mL×3). The filtrate was acidified with 2N HCl to pH ˜2. The organic layer was separated, and the aqueous layer was extracted with EtOAc (50 mL×2). The organic layers were combined and washed with water ((100 mL×2), brine (100 mL) and dried over sodium sulfate. After filtration, heptane (200 mL) was added and the solution was concentrated in vacuo. The resulting precipitate was filtered, washed with heptane (50 mL×2) and dried to afford the desired product (10) (17.09 g) as a light-yellow solid. The mother liquor was concentrated to obtain additional desired product (4.29 g) as a pale-yellow solid. 1H NMR (400 MHz, CDCl3) δ: 7.50 (d, J=15.9 Hz, 1H), 7.09 (d, J=8.3 Hz, 2H), 6.29 (d, J=15.9 Hz, 1H), 5.54 (br, 1H), 4.26 (q, J=7.1 Hz, 2H), 1.33 (t, J=7.1 Hz, 3H).

1. customThe mixture was sealed in the glass tube
2. temperatureThe reaction was cooled to room temperature
3. stirringThe mixture was stirred for 30 minutes
4. filtrationfiltered through celite
5. washrinsed with EtOAc (100 mL×3)
6. customThe organic layer was separated
7. extractionthe aqueous layer was extracted with EtOAc (50 mL×2)
8. washwashed with water ((100 mL×2), brine (100 mL)
9. dry with materialdried over sodium sulfate
10. filtrationAfter filtration, heptane (200 mL)
11. additionwas added
12. concentrationthe solution was concentrated in vacuo
13. filtrationThe resulting precipitate was filtered
14. washwashed with heptane (50 mL×2)
15. customdried