Synthesis
The general procedure for the synthesis of 6-methyl-4-phenylbenzodihydropyran-2-one from p-cresol and trans-cinnamic acid is as follows: a mixture of 0.5 kg cinnamic acid, 0.401 kg p-cresol and 2.2 L xylene was stirred for 15 minutes. 0.132 kg of concentrated sulfuric acid was slowly added under continuous stirring. After addition of the acid, the reaction mixture was stirred at 140-145 °C for the reaction. After completion of the reaction, the reaction was cooled to room temperature and then washed with 1.0 L of deionized water. The reaction mixture was further cooled to 10-15 °C, and 0.5 N NaOH solution was added to deionized water, and the reaction mixture was added dropwise and stirred at the same temperature for 1 hour. The organic layer was separated and washed with deionized water. The organic layer was completely distilled under reduced pressure (30-40 mmHg) to give 3,4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-one (Yield: 0.78 kg, Yield: 97%).HPLC purity: > 95%.
References
[1] Patent: WO2010/46801, 2010, A2. Location in patent: Page/Page column 15
[2] Research on Chemical Intermediates, 2016, vol. 42, # 7, p. 6407 - 6422
[3] Organic Process Research and Development, 2005, vol. 9, # 3, p. 314 - 318
[4] Tetrahedron Letters, 2012, vol. 53, # 33, p. 4469 - 4472
[5] Tetrahedron, 2014, vol. 70, # 34, p. 5221 - 5233