反应详情

温度

55 °C

Well-dried magnesium (3.05 g) and THF (20.0 ml) were put in a reaction vessel under a nitrogen atmosphere, and heated to 55° C. Then, 1-bromo-3-fluoro-4-trifluoromethoxybenzene (T-13; 25.0 g) dissolved in THF (100 ml) was slowly added dropwise thereto in the temperature range of 47° C. to 60° C., and stirred for additional 60 minutes. The obtained Grignard reagent was added dropwise to trimethyl borate (14.0 g) in a THF (100 ml) solution in the temperature range of −74° C. to −65° C., and stirred for additional 180 minutes while allowing temperature to come to 25° C. After the reaction mixture had been cooled to −30° C., 6N-hydrochloric acid (90 ml) was slowly added dropwise and stirred for additional 180 minutes while temperature was allowed to come to 25° C. Then, the reaction mixture was poured into a vessel containing ice-water (250 ml) and 3,000 ml, and mixed. Ethyl acetate (300 ml) was added to separate the mixture into organic and aqueous layers, and an extraction operation was carried out. The obtained organic layer was fractionated, washed sequentially with water, a saturated aqueous solution of sodium bicarbonate and brine, and then dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, whereby 11.7 g of 3-fluoro-4-trifluoromethoxy phenylboronic acid (T-14) was obtained. The yield based on the compound (T-13) was 54%.

1. additionwas slowly added dropwise
2. stirringstirred for additional 180 minutes
3. customto come to 25° C
4. temperatureAfter the reaction mixture had been cooled to −30° C.
5. stirringstirred for additional 180 minutes while temperature
6. customto come to 25° C
7. additionThen, the reaction mixture was poured into a vessel
8. additionmixed
9. customto separate the mixture into organic and aqueous layers
10. washwashed sequentially with water
11. dry with materiala saturated aqueous solution of sodium bicarbonate and brine, and then dried over anhydrous magnesium sulfate
12. distillationThen, the solvent was distilled off under reduced pressure