反应详情

A solution of 3,5-difluoro-2-nitrobenzoic acid (522 mg, 2.57 mmol) in DCM (10 mL) was treated with oxalyl chloride (0.337 mL, 3.86 mmol), then with DMF (3 drops). The resulting solution was stirred at room temperature for 60 min. The mixture was concentrated and the residue was re-concentrated twice from dry DCM. The residue was dissolved in DCM (10 mL) and treated dropwise with 3-bromo-2-methylaniline (478 mg, 2.57 mmol), followed by dropwise addition of TEA (0.537 mL, 3.86 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was treated with saturated aqueous NaHCO3, forming a white precipitate. The organic phase was separated, and the aqueous phase and the white solid were extracted twice with DCM, then filtered. The collected solid was washed with water and dried. The combined organic phases were dried and concentrated, and the residue was triturated with DCM to give additional solid. Both solids were combined with DCM and MeOH and concentrated to give N-(3-bromo-2-methylphenyl)-3,5-difluoro-2-nitrobenzamide (821 mg, 86% yield). Mass spectrum m/z 371, 373 (M+H)+393, 395 (M+Na)+. 1H NMR (400 MHz, DMSO-d6) δ 10.65 (s, 1H), 7.98-7.90 (m, 1H), 7.81 (d, J=8.1 Hz, 1H), 7.55 (d, J=7.9 Hz, 1H), 7.40 (d, J=7.7 Hz, 1H), 7.21 (t, J=7.9 Hz, 1H), 2.32 (s, 3H).

1. concentrationThe mixture was concentrated
2. concentrationthe residue was re-concentrated twice from dry DCM
3. dissolutionThe residue was dissolved in DCM (10 mL)
4. stirringThe resulting mixture was stirred at room temperature overnight
5. customforming a white precipitate
6. customThe organic phase was separated
7. extractionthe aqueous phase and the white solid were extracted twice with DCM
8. filtrationfiltered
9. washThe collected solid was washed with water
10. customdried
11. customThe combined organic phases were dried
12. concentrationconcentrated
13. customthe residue was triturated with DCM
14. customto give additional solid
15. concentrationconcentrated