反应详情

温度

85 °C

Under a nitrogen atmosphere, a solution of 18 (66 g, 0.15 mol) in anhydrous DMF (350 mL) was charged with (n-Bu)4NCl (41.5 g, 0.15 mol), K2CO3 (20.6 g, 0.15 mol), NaHCO2 (10.2 g, 0.15 mol), and Pd(OAc)2 (3.35 g, 0.015 mol) at ambient temperature. The heterogeneous mixture was immersed in a pre-heated (85° C.) oil bath. After 1 h, TLC analysis revealed some 18 remained therefore more catalyst (1 g) was added. After 1.5 h, another charge of catalyst (0.6 g) was added. After an additional 1.5 h of heating, 18 had been completely consumed by TLC analysis [TLC analysis, 2% MeOH/DCM, Rf(18)=0.7; Rf(19)=0.8]. The warm reaction mixture was transferred to an ice water bath to cool then diluted with diethyl ether and filtered through a pad of celite. The solids were washed with diethyl ether and the filtrate was washed several times with water to remove DMF then once with brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 52.5 g of crude 19, which was used without further purification. 1H NMR (CDCl3, 300 MHz) δ8.18 (m, 1H), 7.60 (m, 1H), 7.18 (m, 1H), 7.05 (dt, J=2.4, 8.7 Hz, 1H), 4.13 (m, 1H), 3.41 (m, 1H), 3.33 (m, 2H), 3.17 (app dd, J=14.1, 38.1 Hz, 1H), 2.61 (s, 3H), 1.83 (m, 3H), 1.69 (m, 1H), 1.49 (s, 9H) ppm.

1. waitAfter 1.5 h
2. additionwas added
3. temperatureAfter an additional 1.5 h of heating
4. custom18 had been completely consumed by TLC analysis [TLC analysis, 2% MeOH/DCM, Rf(18)=0.7; Rf(19)=0.8]
5. customThe warm reaction mixture
6. customwas transferred to an ice water bath
7. temperatureto cool
8. filtrationfiltered through a pad of celite
9. washThe solids were washed with diethyl ether
10. washthe filtrate was washed several times with water
11. customto remove DMF
12. dry with materialonce with brine, dried over anhydrous Na2SO4
13. filtrationfiltered
14. concentrationconcentrated
15. customto afford 52.5 g of crude 19, which
16. customwas used without further purification