反应详情

温度

110 °C

A mixture of 3-chloro-2-methylbenzoic acid (100 g, 0.58 mol), N-chlorosuccinimide (90 g, 0.67 mol) and palladium (II) acetate (14.7 g, 65.7 mmol) in N,N-dimethylformamide (1 L) was stirred at 110° C. under a nitrogen atmosphere overnight. After cooling to room temperature, cesium carbonate (378 g, 1.16 mol) and iodoethane (317 g, 2.03 mol) were added and stirring continued at room temperature for 1.5 hours. The reaction mixture was poured into a mixture of water (1 L) and methyl tert-butyl ether (800 mL). Solids were removed by filtration, and the filtrate layers separated. The aqueous layer was extracted with more methyl tert-butyl ether (600 mL). The combined organic extracts were washed with saturated aqueous sodium chloride solution (1.2 L), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography (eluting with 50:1 petroleum ether/ethyl acetate), affording ethyl 3,6-dichloro-2-methylbenzoate (253b, 110 g, ˜80% pure, 80% yield) as a yellow oil.

1. temperatureAfter cooling to room temperature
2. stirringstirring
3. waitcontinued at room temperature for 1.5 hours
4. customSolids were removed by filtration
5. customthe filtrate layers separated
6. extractionThe aqueous layer was extracted with more methyl tert-butyl ether (600 mL)
7. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution (1.2 L)
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated in vacuo
10. customThe residue was purified by silica gel chromatography (eluting with 50:1 petroleum ether/ethyl acetate)