反应详情

Dry tetrahydrofuran (10 ml) was added to 3-trifluoromethyl-4-bromo-1-methoxybenzene (compound III) (4.4 g) and metallic magnesium (0.41 g) and thereto was further added a catalytic amount of iodine, followed by refluxing for 1.5 hours with stirring. After the temperature was returned to room temperature, to the mixture was slowly added dropwise a solution prepared by adding dry ice (30 g) to dry tetrahydrofuran (10 ml) at -40° C. or lower. The temperature was returned to room temperature and then the reaction was allowed to proceed for further 2 hours. Then, the reaction mixture was added to 1N hydrochloric acid (50 ml) to stop the reaction and repeatedly extracted with ethyl acetate. The ethyl acetate layer was sufficiently washed with water and dried by adding anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure and then, the resulting solid was recrystallized from methylene chloride to obtain 2-trifluoromethyl-4-methoxybenzoic acid (compound IV, 1.5 g).

1. temperatureby refluxing for 1.5 hours
2. customwas returned to room temperature, to the mixture
3. additionwas slowly added dropwise a solution
4. customprepared
5. customwas returned to room temperature
6. customthe reaction
7. extractionrepeatedly extracted with ethyl acetate
8. washThe ethyl acetate layer was sufficiently washed with water
9. customdried
10. additionby adding anhydrous sodium sulfate
11. customThe solvent was removed by distillation under reduced pressure
12. customthe resulting solid was recrystallized from methylene chloride