反应详情

温度

60 °C

5-Chloro-2,4-difluorobenzoic acid (1.17 g, 6.08 mmol) was dissolved in thionyl chloride (5.0 mL) and heated at 60° C. under a nitrogen atmosphere for 5 hours. The reaction mixture was concentrated in vacuo and azeotroped with DCM (2×10 mL) and toluene (10 mL). Then the crude was dissolved in DCM (15 mL) and cooled to 0° C. 4-Methylphenol (0.665 g, 6.15 mmol) and triethylamine (1.05 mL, 7.53 mmol) in DCM (10 mL) were added dropwise and the reaction mixture was stirred at room temperature under a nitrogen atmosphere for 18 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in EtOAc (10 mL), then washed with saturated aqueous solution of sodium hydrogencarbonate (2×10 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo to yield the crude solid. The solid was triturated in the minimum amount of heptanes to afford the title compound as a white solid (1.20 g, 69%):

1. concentrationThe reaction mixture was concentrated in vacuo
2. customazeotroped with DCM (2×10 mL) and toluene (10 mL)
3. dissolutionThen the crude was dissolved in DCM (15 mL)
4. temperaturecooled to 0° C
5. concentrationThe reaction mixture was concentrated in vacuo
6. dissolutionthe residue dissolved in EtOAc (10 mL)
7. washwashed with saturated aqueous solution of sodium hydrogencarbonate (2×10 mL)
8. dry with materialThe organic layer was dried over sodium sulfate
9. concentrationconcentrated in vacuo
10. customto yield the crude solid
11. customThe solid was triturated in the minimum amount of heptanes