Synthesis
GENERAL METHOD: m-Trifluoromethylphenol (150 mmol) was dissolved in glacial acetic acid (50 mL), stirred and the reaction temperature was maintained at 40 °C. Subsequently, a mixed solution consisting of 11 mL of 65% HNO3 and 30 mL of glacial acetic acid was slowly added dropwise over 15 minutes. After the dropwise addition was completed, the reaction mixture was continued to be stirred at room temperature for 45 minutes. Upon completion of the reaction, the mixture was quenched by pouring it into ice water (400 mL). The aqueous phase was extracted four times with chloroform (100 mL). The organic phases were combined, dried with anhydrous sodium sulfate, concentrated under reduced pressure and purified by column chromatography (for 4a, 4c, 4e) or recrystallized from ethanol (for 4b). Compound 4d can be used directly in subsequent reactions without further purification [17].
References
[1] Organic Letters, 2008, vol. 10, # 14, p. 3025 - 3028
[2] European Journal of Medicinal Chemistry, 2012, vol. 56, p. 108 - 119
[3] Chemistry - A European Journal, 2011, vol. 17, # 33, p. 9076 - 9082
[4] Journal of Organic Chemistry, 1991, vol. 56, # 5, p. 1788 - 1800
[5] Patent: WO2006/5909, 2006, A1. Location in patent: Page/Page column 52
