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Part A. Preparation of 2-tert-butyl-4-nitrophenol. Under vigorous stirring conditions, 70% nitric acid (4.25 mL, 66.6 mmol) was diluted with water (4.25 mL) and added dropwise rapidly to a solution of 2-tert-butylphenol (10 g, 66.6 mmol) in heptane (67 mL). The reaction mixture took on a deep red to brown color and continued to stir vigorously for 2 hours. Upon completion of the reaction, the suspended solid product was collected by filtration and washed sequentially with hexane (300 mL), water (200 mL) and again with hexane (200 mL). The final product was obtained as a cocoa-colored powder, dried to constant weight in a yield of 4.65 g in 35.6% yield.

[1] Patent: WO2009/39127, 2009, A1. Location in patent: Page/Page column 164; 170; 175-176; 226
[2] Patent: WO2009/39134, 2009, A1. Location in patent: Page/Page column 98; 104-105
[3] Patent: WO2009/39135, 2009, A1. Location in patent: Page/Page column 100; 119
[4] Journal of Medicinal Chemistry, 2018, vol. 61, # 3, p. 1153 - 1163