反应详情

To a solution of 5-amino-2-fluorobenzoic acid (89.6 g, 577 mmol) in MeOH (1000 mL) was added sulfurous dichloride (82.4 g, 692 mmol) dropwise at 0° C. Then the mixture was heated to reflux for overnight. The solvent was removed. The residue was diluted with EtOAc (1 L). Then the pH was adjusted to around 9 by progressively adding saturated NaHCO3. The organic layer was separated. The aqueous layer was extracted with EtOAc (500 L×3). The combined organic layers were washed with water and brine successively, dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound of step A (79.8 g, 81.8% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.16-7.20 (m, 1H), 6.90-6.98 (m, 1H), 6.75-6.82 (m, 1H), 3.89 (s, 3H), 3.51-3.70 (br, 2H).

1. temperatureThen the mixture was heated
2. temperatureto reflux for overnight
3. customThe solvent was removed
4. additionThe residue was diluted with EtOAc (1 L)
5. customThe organic layer was separated
6. extractionThe aqueous layer was extracted with EtOAc (500 L×3)
7. washThe combined organic layers were washed with water and brine successively
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure