反应详情

温度

-75 °C

A solution of TMEDA (10.5 mL, 70 mmol) in THF (50 mL) was cooled to <−80° C. and treated with sec-butyllithium (50 mL, 70 mmol). A solution of 2,4-difluorobenzoic acid (5.0 g, 31.6 mmol) in THF was added dropwise maintaining the temperature below −80° C. The reaction mixture was allowed to warm to −75° C. and treated with DMF (15 mL), the mixture then allowed to warm to 0° C. before quenching the reaction with water. The aqueous layer was separated, acidified to pH ˜2 (concentrated HCl) and extracted twice with diethyl ether. The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to give a yellow oil. The crude product was crystallized from cyclohexane/diethyl ether to give the title compound as a yellow solid (670 mg, 11%). 1H NMR (CDCl3, 400 MHz) 10.40 (1 H, s), 8.31 (1 H, ddd, J=8.96, 8.02, 6.08 Hz), 7.12 (1 H, td, J=9.09, 1.42 Hz).

1. temperaturemaintaining the temperature below −80° C
2. temperatureto warm to 0° C.
3. custombefore quenching
4. customthe reaction with water
5. customThe aqueous layer was separated
6. extractionextracted twice with diethyl ether
7. dry with materialThe combined organic extracts were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto give a yellow oil
11. customThe crude product was crystallized from cyclohexane/diethyl ether