Sodium Hydroxide → 2-Methyl-4-((2-methylbenzoyl)amino)benzoic acid

Participants

Reaction Conditions

Reaction Steps

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 60° C. to give the crude product (58.33 g). To the crude product (29.17 g) are added 2.5 mol/L aqueous sodium hydroxide solution (400 mL) and toluene (100 mL), and insoluble materials are removed by filtration and then separated into two layers. The aqueous layer is washed twice with toluene (100 mL) and neutralized with 6 mol/L hydrochloric acid (300 mL). The precipitated crystals are separated by filtration and dried at 60° C. and then recrystallized from methanol (540 mL) to give the desired product (19.67 g, yield 65.8%, purity by HPLC 99.4%).

Provenance & Evidence