反应详情

To a solution of 2-chloro-6-fluoro-3-methoxy-benzoic acid (2.7 g, 13.2 mmol, 1.0 eq) in a mixture of DCM (20 mL) and DMF (3 drops) at 0° C. was added (COCl)2 (5.0 g, 39.6 mmol, 3.0 eq) dropwise. The reaction mixture was stirred at room temperature for 1 h, and then concentrated to dryness; the residue was dissolved in acetone (20 mL) and added dropwise to a solution of NaN3 (2.6 g, 39.6 mmol, 3.0 eq) in water (15 mL) at 0° C. The reaction was stirred 1 h at 0° C., water (50 mL) was added, then the reaction heated at 70° C. overnight. The acetone was removed by distillation and the aqueous residue extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo to give a residue, which was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:30) to give the title compound as a yellow oil (0.85 g, 37%).

1. concentrationconcentrated to dryness
2. dissolutionthe residue was dissolved in acetone (20 mL)
3. stirringThe reaction was stirred 1 h at 0° C.
4. temperaturethe reaction heated at 70° C. overnight
5. customThe acetone was removed by distillation
6. extractionthe aqueous residue extracted with EtOAc
7. washThe combined organic extracts were washed with water and brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customevaporated in vacuo
11. customto give a residue, which
12. customwas purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:30)