Synthesis
1. 2-Chloro-4-fluoro-5-nitrotoluene (260 g) and potassium hydroxide (116 g) were added to 1.5 L of isopropanol and the reaction was carried out at 20 °C. The progress of the reaction was monitored by TLC until the disappearance of the raw material. 2. After completion of the reaction, the stirring was stopped, and the reaction solution was slowly poured into 5 L of water. 3. The reaction mixture was filtered, and the solid product was collected and washed with an appropriate amount of water. 4. The filter cake was dried. 1-chloro-5-isopropoxy-2-methyl-4-nitrobenzene (271 g) was obtained in 86.3% yield.
References
[1] Journal of Medicinal Chemistry, 2013, vol. 56, # 14, p. 5675 - 5690
[2] Patent: EP3287463, 2018, A1. Location in patent: Paragraph 0164; 0165
[3] Patent: CN106674084, 2017, A. Location in patent: Paragraph 0026; 0027; 0028
[4] Patent: CN106336398, 2017, A. Location in patent: Paragraph 0108; 0127; 0128; 0129
[5] Patent: CN106478700, 2017, A. Location in patent: Paragraph 0093; 0108; 0109; 0110
