Synthesis
General procedure for the synthesis of 4-(5-methyl-3-phenyl-4-isoxazolyl)benzenesulfonyl chloride from 5-methyl-3,4-diphenyl-isoxazole: Dichloromethane was added to the reactor and cooled to 10-15 °C, and 98.00 kg of chlorosulfonic acid was slowly added. 3,4-Diphenyl-5-methylisoxazole was dissolved in 50 liters of dichloromethane and slowly added to the reaction material at 0-10°C, followed by heating and refluxing for 9-11 hours. Upon completion of the reaction, the reaction material was cooled to 25-35°C. The reaction material was slowly added to 175 liters of cold water at 0-10°C and the temperature was raised to 25-35°C. The aqueous and organic layers were separated and the aqueous layer was extracted with 125 liters of dichloromethane in two batches. The organic layer was combined and washed three times with 575 liters of water. The combined organic layers were added to a reactor and the dichloromethane was removed by distillation below 60°C. The crude solid obtained was dissolved in 250 liters of cyclohexane and heated to reflux for 30-45 minutes. Subsequently, water was added to the reaction material and heated to reflux again for 15-30 minutes, and the organic layer and the underlying aqueous layer were separated after the reaction material settled. The organic layer was cooled to 25-35°C, maintained at this temperature for 45-60 minutes and then filtered and washed with cyclohexane. This washing process was repeated twice. Finally, the wet compound was dried at 50-55°C to give 4-(5-methyl-3-phenyl-4-isoxazole)benzenesulfonyl chloride (yield 21.3 kg, 59.15%).
References
[1] Synthetic Communications, 2012, vol. 42, # 5, p. 639 - 649
[2] Patent: EP1550658, 2005, A1. Location in patent: Page/Page column 7
[3] Patent: WO2005/123701, 2005, A1. Location in patent: Page/Page column 38-39
[4] Patent: US2003/105334, 2003, A1
[5] Patent: CN105367508, 2016, A. Location in patent: Paragraph 0038; 0045
