反应详情

温度

-78 °C

n-Butyllithium (2.5M solution in hexanes, 67.6 mL, 169 mmol) was added slowly to a stirred, cooled (−78° C.) solution of 3,5-bis(trifluoromethyl)benzeneacetic acid (20.0 g, 73.5 mmol) in tetrahydrofuran (400 mL) and the mixture was stirred at −78° C. for 1 hour. Iodomethane (6.87 mL, 110 mmol) was added slowly and the mixture was allowed to warm to room temperature and stirred overnight. Aqueous sodium bisulfite (20%) was added until the mixture was acidic. The mixture was extracted with ethyl acetate, the combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (400 mL), dicyclohexylamine (10 mL, 80.85 mmol) was added and the mixture was heated under reflux for 1 hour. The mixture was cooled and the solid was collected and dried in vacuo to give the title compound as a colorless solid (31.13 g, 91%). 1H NMR (400 MHz, CDCl3) δ 7.83 (2H, s), 7.68 (1H, s), 3.66 (1H, q, J 7.1 Hz), 2.83–2.75 (2H, m), 1.87–1.84 (4H, m), 1.71–1.68 (4H, m), 1.60–1.57 (2H, m), 1.48 (3H, d, J 7.1 Hz), 1.28–1.08 (8H, m), and 1.03–0.92 (2H, m).

1. temperatureto warm to room temperature
2. stirringstirred overnight
3. extractionThe mixture was extracted with ethyl acetate
4. dry with materialthe combined organic fractions were dried (MgSO4)
5. customthe solvent was evaporated under reduced pressure
6. dissolutionThe residue was dissolved in ethyl acetate (400 mL)
7. temperaturethe mixture was heated
8. temperatureunder reflux for 1 hour
9. temperatureThe mixture was cooled
10. customthe solid was collected
11. customdried in vacuo