反应详情

温度

25 °C

A solution of 3-fluoro-4-methyl-benzoic acid (2.5 g, 16.2 mmol) in acetone (27.0 mL) was treated with potassium carbonate (5.83 g, 42.2 mmol) and dimethyl sulfate (6.14 g, 4.6 mL, 48.7 mmol). The reaction was stirred at 25° C. for 24 h and then was heated to 90° C. for 8 h. At this time, the reaction was cooled to 25° C. and was stirred at 25° C. for 6 days. At this time, the reaction was filtered through a sintered glass funnel. The potassium carbonate cake was washed thoroughly with acetone. The filtrate was concentrated in vacuo. The residue was then taken up in ethyl acetate (30 mL) and triethylamine (7 mL) and stirred at 25° C. for 30 min. The solution was then transferred to a separatory funnel and washed with water (1×75 mL), a 2N aqueous hydrochloric acid solution (1×75 mL), and a saturated aqueous sodium chloride solution (1×75 mL), dried over sodium sulfate, filtered and concentrated in vacuo to afford 3-fluoro-4-methyl-benzoic acid methyl ester (2.26 g, 82.9%) as a light yellow oil. ES+-HRMS m/e calcd for C9H9O2F [M+H+] 169.0660. Found 169.0659. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.70 (dd, J=7.8, 1.5 Hz, 1H) 7.62 (dd, J=10.3, 1.5 Hz, 1H) 7.46 (t, J=7.8 Hz, 1H) 3.85 (s, 3H) 2.31 (d, J=1.5 Hz, 3H).

1. temperaturewas heated to 90° C. for 8 h
2. temperatureAt this time, the reaction was cooled to 25° C.
3. stirringwas stirred at 25° C. for 6 days
4. filtrationAt this time, the reaction was filtered through a sintered glass funnel
5. washThe potassium carbonate cake was washed thoroughly with acetone
6. concentrationThe filtrate was concentrated in vacuo
7. stirringtriethylamine (7 mL) and stirred at 25° C. for 30 min
8. customThe solution was then transferred to a separatory funnel
9. washwashed with water (1×75 mL)
10. dry with materiala 2N aqueous hydrochloric acid solution (1×75 mL), and a saturated aqueous sodium chloride solution (1×75 mL), dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo