Synthesis
The general procedure for synthesizing 2-trifluoromethoxy-5-bromobenzonitrile from 5-bromo-2-(trifluoromethoxy)benzaldehyde is as follows (reference Example 85): to a solution of 5-bromo-2-(trifluoromethoxy)benzaldehyde (2.00 g, 7.43 mmol) and hydroxylamine hydrochloride (568 mg, 8.18 mmol) in DMF (7.5 mL), was added sequentially triethylamine ( 1.14 mL, 8.18 mmol) and propylphosphonic anhydride (cyclic trimer, ~1.7 M ethyl acetate solution, 4.8 mL, 8.18 mmol). The reaction mixture was stirred at 100°C for 8 hours. Upon completion of the reaction, the reaction solution was poured into saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layers were combined, washed with brine and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate=100/0-98/2] to afford the target product 2-trifluoromethoxy-5-bromobenzonitrile (1.71 g, yield: 86%).1H-NMR (400 MHz, CDCl3) δ: 7.85 (1H, d, J=3Hz), 7.78 (1H. dd, J=9,3Hz), 7.31-7.27 (1H, m).
References
[1] Patent: EP2862861, 2015, A1. Location in patent: Paragraph 0586; 0587; 0588
[2] Patent: JP2015/113323, 2015, A. Location in patent: Paragraph 0541 - 0543
