反应详情

To a solution of 2-chloro-3-(trifluoromethyl)benzoic acid (5.26 g, 23.4 mmol) in tetrahydrofuran (50 mL) were added N,N-dimethylformamide (40 μL) and oxalyl chloride (2.8 mL, 31.9 mmol), and the mixture was stirred at room temperature for 2 hr. The solvent was evaporated under reduced pressure to give 2-chloro-3-(trifluoromethyl)benzoyl chloride. To a solution of 5-amino-2-methylphenol (2.62 g, 21.2 mmol) in tetrahydrofuran (20 mL) was added water (30 mL) in which sodium hydrogen carbonate (2.68 g, 31.9 mmol) has been suspended, and the mixture was vigorously stirred at room temperature. To the mixture was added dropwise a solution of 2-chloro-3-(trifluoromethyl)benzoyl chloride produced above in tetrahydrofuran (30 mL) under ice-cooling, and the mixture was stirred at room temperature for 18 hr. The aqueous layer of the reaction mixture was separated, and the organic layer was diluted with ethyl acetate, and washed with saturated brine. The extract was dried over anhydrous magnesium sulfate, and filtered through a pad filled with silica gel. The solvent was concentrated under reduced pressure, and the obtained solid was washed with a mixed solvent of ethyl acetate and hexane to give the title compound (6.37 g, 91%) as a pale-brown powder. The obtained compound was used for the next reaction without further purification operation.

1. temperaturecooling
2. stirringthe mixture was stirred at room temperature for 18 hr
3. customThe aqueous layer of the reaction mixture was separated
4. additionthe organic layer was diluted with ethyl acetate
5. washwashed with saturated brine
6. dry with materialThe extract was dried over anhydrous magnesium sulfate
7. filtrationfiltered through a pad
8. additionfilled with silica gel
9. concentrationThe solvent was concentrated under reduced pressure
10. washthe obtained solid was washed with a mixed solvent of ethyl acetate and hexane