2-(Bromodifluoromethyl)-1,3-benzoxazole synthesis

Yield: 85%

Reaction Conditions:

Stage #1:bromodifluoroacetic acid with carbon tetrabromide;triethylamine;triphenylphosphine in toluene at 0; for 0.166667 h;Inert atmosphere;
Stage #2:2-amino-phenol in toluene for 8 h;Inert atmosphere;Reflux;

Steps:

4.2. General procedure for preparation of 2-bromodifluoromethyl benzo-1,3-diazoles (2)
General procedure: A 200-ml three-necked flask equipped with a condenser was charged with Ph₃P (2.20 g, 8.4 mmol), Et₃N (0.85 g, 8.4 mmol), CBr₄ (16.8 g, 8.4 mmol), and bromodifluoro acetic acid (2.8 mmol) in toluene (10.0 ml) at 0 °C under nitrogen atmosphere. After the solution was stirred for about 10 min (ice water bath), 2-amino phenol (3.3 mmol) dissolved in toluene (5.0 ml) was added dropwise. The mixture was refluxed under stirring for 6-24 h. Solvent was evaporated under reduced pressure, and the residue was diluted with petroleum ether (60-90 °C) and filtered. The residual solid of Ph₃PO and Et₃N·HCl was washed with petroleum ether 3 times. The filtrate was concentrated; the residue was then purified by column chromatography to obtain the product 2.

References:

Jiang, Haizhen;Yuan, Shijie;Cai, Yeshan;Wan, Wen;Zhu, Shizheng;Hao, Jian [Journal of Fluorine Chemistry,2012,vol. 133,p. 167 - 170] Location in patent:experimental part