4-(2-Methylbenzoylamino)-2-methylbenzoic acid

off-white to white powder

Preparation of 2-methyl-4-(2-methylbenzoylamino)benzoic acid; To a solution of 3-(2-methylbenzoylamino)toluene (50.0 g, 0.222 mole) in methylene chloride (50 mL) which is cooled to 3°C is added aluminum chloride (88.8 g, 0.666 mole) under nitrogen atmosphere over a period of about 10 minutes. The mixture is cooled to 3°C, and thereto is added dropwise oxalyl chloride (25.2 mL, 0.289 mole) at 3-7°C. The mixture is stirred at 2-7°C for 5 hours. After confirming the disappearance of the starting materials, the reaction mixture is diluted with methylene chloride (100 mL), and thereto is added ice water to quench the reaction. After distilling off methylene chloride, the resulting aqueous suspension is refluxed for 30 minutes and then cooled to room temperature. The resulting crystals are separated by filtration and the wet crystals are dried at 60Preparation of 2-methyl-4-(2-methylbenzoylamino)benzoic acid; 2-Methyl-4-(2-methylbenzoylamino)acetophenone (1000 g, 3.74 mole) is dissolved in isopropyl alcohol (5 L) by heating at 50 to 60°C. The solution is cooled to below 5° C, thereto is added dropwise 12 percent(w/w) aqueous sodium hypochlorite solution (7665 g, 25.8 mole as an active chlorine (Cl)) with attention not to be over 10Preparation of 2-methyl-4~(2-methylbenzoylamino)benzoic acid; A toluene solution of a mixture of 2-chloro-2-methyl-4-(2-methyl- benzoylaminojacetophenone and 2-chloro-4-methyl-2-(2-methyl- benzoylamino)acetophenone obtained in the above Reference Example 5 is concentrated and to the residue is added isopropyl alcohol (twice volume). To the mixture is added dropwise an aqueous sodium hypochlorite solution (twice molar amount) at 10-20Preparation of 2-methyl-4-(2-methylbenzoylamino)benzoic acid; The isomer mixture of l-{2-[2-methyl-4-(2-methylbenzoylamino)- phenyl]-2-oxoethyl}pyridinium chloride and l-{2-[4-methyl-2-(2- methylbenzoylamino)phenyl]-2-oxoethyl}pyridinium chloride obtained in the above Reference Example 6 (207.3g