反应详情

温度

75 °C

To a solution of 4-chloro-5-iodo-2-methylbenzoic acid (compound 177.1, 20.0 g, 67.5 mmol, 1.00 equiv) in methanol (100 mL) was added sulfuric acid (5 mL) dropwise. The resulting mixture was stirred overnight at 75° C. After cooling to ambient temperature, the methanol was removed under reduced pressure. The pH value of the remaining aqueous layer was carefully adjusted to 7 with sodium bicarbonate (aq., 1 M. Note: significant gas evolution). The aqueous phase was extracted with 2×200 mL of ethyl acetate and the combined organic layers were washed with 2×100 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:50) as eluent to furnish 20.0 g (95%) of methyl 4-chloro-5-iodo-2-methylbenzoate as a light yellow liquid.

1. temperatureAfter cooling to ambient temperature
2. customthe methanol was removed under reduced pressure
3. extractionThe aqueous phase was extracted with 2×200 mL of ethyl acetate
4. washthe combined organic layers were washed with 2×100 mL of brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under vacuum
7. customThe residue was purified