反应详情

温度

105 °C

To 1-methylpiperazine (980 μl, 8.80 mmol) in toluene (15 ml) was added tris(dibenzylidene acetone)dipalladium (201 mg, 0.22 mmol), BINAP (550 mg, 0.88 mmol), and cesium carbonate (4.30 g, 13.2 mmol). The mixture was stirred for 30 minutes before the addition of methyl 4-bromo-3-fluorobenzoate (2.05 g, 8.80 mmol), after which, the temperature was increased to 105° C. and stirred for an additional 18 h. The mixture was cooled and filtered through Celite, washed with ethyl acetate, and the resultant filtrate concentrated in vacuo to afford an orange oil. The residue was purified by column chromatography eluting with 5% methanol in dichloromethane. Pure fractions were concentrated to afford (1.80 g, 81%) of methyl 3-fluoro-4-(4-methylpiperazin-1-yl)benzoate as a colorless oil. 1H NMR (400 MHz, CD3OD): 7.78-7.73 (d, 1H), 7.64-7.59 (d, 1H), 7.09-7.03 (m, 1H), 3.86 (s, 3H), 3.26-3.20 (m, 4H), 2.65-2.59 (m, 4H), 2.35 (s, 3H). MS (EI) for C13H17FN2O2: 253 (MH+).

1. temperatureThe mixture was cooled
2. filtrationfiltered through Celite
3. washwashed with ethyl acetate
4. concentrationthe resultant filtrate concentrated in vacuo
5. customto afford an orange oil
6. customThe residue was purified by column chromatography
7. washeluting with 5% methanol in dichloromethane
8. concentrationPure fractions were concentrated