Uses
2-Bromo-1-(3-(trifluoromethyl)phenyl)ethyl ketone is a trifluoromethoxylated compound with high membrane permeability, anti-metabolic stability, affinity for lipid membranes, thermal stability, and chemical stability, and is widely used in the pharmaceutical and chemical industries.
Synthesis
The general procedure for the synthesis of 2-bromo-1-(3-(trifluoromethyl)phenyl)ethanone from 3-(trifluoromethyl)acetophenone was as follows: to a toluene solution (423 mL) of 3-(trifluoromethyl)acetophenone (79.6 g, 0.423 mol) was slowly added pyridinium perbromide (135.4 g, 0.423 mol) under ice-bath cooling conditions. The reaction mixture was stirred for 5 hours, during which time it was allowed to warm up naturally to room temperature. Upon completion of the reaction, the reaction solution was again cooled in an ice bath, followed by slow dropwise addition of distilled water (400 mL) to quench the reaction. Next, the toluene layer was washed with saturated aqueous sodium bicarbonate (400 mL), followed by drying the organic phase with anhydrous magnesium sulfate. The dried organic phase was concentrated under reduced pressure and then purified by reduced pressure distillation to afford the target product 2-bromo-1-(3-(trifluoromethyl)phenyl)ethanone (92.35 g, 81.7% yield). The product was characterized by 1H-NMR (200 MHz, TMS, CDCl3): δ 4.46 (2H, s), 7.66 (1H, brt, J = 7.9 Hz), 7.88 (1H, brd, J = 7.6 Hz), 8.19 (1H, brd, J = 5.5 Hz), 8.25 (1H, brs). The boiling point was 92°C/3 mmHg.
References
[1] Journal of Medicinal Chemistry, 1995, vol. 38, # 1, p. 34 - 41
[2] Journal of Organic Chemistry, 1980, vol. 45, # 24, p. 4989 - 4990
[3] Journal fuer Praktische Chemie/Chemiker-Zeitung, 1998, vol. 340, # 7, p. 649 - 655
[4] Journal of Medicinal Chemistry, 2014, vol. 57, # 15, p. 6572 - 6582
[5] Patent: EP1571148, 2005, A1. Location in patent: Page/Page column 28
