反应详情

3-Amino-2,4,5-trifluoro-benzoic acid (commerically available) (12.5 g, 65.50 mmol) was heated with thionyl chloride (110 ml) at 90° C. for 2 hours under a nitrogen atmosphere. The excess thionyl chloride was removed in vacuo. To a solution of the residue (13.37 g, 52.30 mmol) in dichloromethane (218 ml) under a nitrogen atmosphere was added a solution of 2,6-dimethyl-4-(heptafluoroprop-2-yl)aniline (prepared according to EP 1,006,102) (15.12 g, 52.30 mmol) in pyridine (4.2 ml, 52.30 mmol). The reaction mixture was stirred at ambient temperature for 2 hours and then extracted with aqueous hydrochloric acid (1M). The aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed with aqueous sodium hydrogen carbonate (1M), dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 7:3) to give 3-amino-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-2,4,5-trifluoro-benzamide (18.4 g, 76% yield). 1H-NMR (400 MHz, CDCl3): 2.35 (6H, s), 4.07 (2H, bs), 7.3-7.35 (1H, m), 7.36 (2H, s), 7.83 (1H, d) ppm.

1. customThe excess thionyl chloride was removed in vacuo
2. extractionextracted with aqueous hydrochloric acid (1M)
3. extractionThe aqueous phase was extracted twice with dichloromethane
4. washThe combined organic phases were washed with aqueous sodium hydrogen carbonate (1M)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated
7. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 7:3)