4-[(Biphenyl-2-ylcarbonyl)amino]benzoic acid

Synthesis

Thionyl chloride (10.4 g, 87.4 mmol) was added to a mixture of biphenyl-2-carboxylic acid (15.0 g, 75.7 mmol) and DMF (0.28 g, 3.83 mmol) in toluene (72 mL) at an internal temperature of 40 ºC. The mixture was stirred at this temperature for approximately 2 h. After completion of the reaction, the mixture was concentrated to dryness at 60 ºC. The resultant residue was then diluted with toluene (36 mL) and concentrated to dryness at 60 ºC, and the process was repeated again to give biphenyl-2- carbonyl chloride as an oil. Acetone (100 mL) was added to the oil, and 4-amino benzoic acid (10.4 g, 75.8 mmol) and N,N-dimethylaniline (10.1 g, 83.3 mmol) were added to the resultant solution at 25 ºC. The mixture was stirred at this temperature for approximately 2 h. Water (100 mL) was then poured into the mixture, and it was stirred at 25 ºC for more than 1 h. The resultant crystals were collected by fifiltration and dissolved in DMF (100 mL) at 25 ºC. The solution was then fifiltered to remove insoluble materials, water (100 mL) was poured into the fifiltrate, and it was stirred at 25 ºC for approximately 2 h. The resultant crystals were collected by fifiltration and dried at 40 ºC to give the amide as white crystals (22.7 g, 95%).

Reference: Tsunoda, T.; Yamazaki, A.; Mase, T.; Sakamoto, S. Org. Process Res. Dev. 2005, 9, 593–598.