反应详情

温度

100 °C

To 5-bromo-4-fluoro-2-nitrophenyl methyl ether (4.0 g, 16.0 mmol) in dioxane (150 mL) was added 1-(1-methylethyl)piperazine (4.1 g, 32.0 mmol), XANTPHOS (0.9 g, 1.6 mmol), and Cs2CO3 (10.4 g, 32.0 mmol). The mixture was bubbled with N2 for 15 min prior to the addition of Pd2(dba)3 (0.7 g, 0.8 mmol). The reaction was stirred at 100° C. for 18 h. Ethyl acetate (100 mL) was used to dilute the reaction mixture, followed by the addition of water (80 mL). After partitioning, extraction with Ethyl acetate (2×75 mL), drying (Na2SO4), filtration and concentration, silica gel chromatography afforded 1-[2-fluoro-5-(methyloxy)-4-nitrophenyl]-4-(1-methylethyl)piperazine as a yellow solid (3.3 g, 70% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.98 (d, J=6.6 Hz, 6 H), 2.54-2.61 (m, 4 H), 2.68 (dt, J=13.2, 6.6 Hz, 1 H), 3.24-3.31 (m, 4 H), 3.91 (s, 3 H), 6.64 (d, J=7.7 Hz, 1 H), 7.82 (d, J=13.6 Hz, 1 H).

1. customThe mixture was bubbled with N2 for 15 min
2. additionto dilute the reaction mixture
3. customAfter partitioning
4. extractionextraction with Ethyl acetate (2×75 mL)
5. customdrying
6. filtration(Na2SO4), filtration and concentration, silica gel chromatography