Synthesis
The general procedure for the synthesis of 2-phenyl-3-hydroxy-5-trifluoromethyl-2H-pyrazole from phenylhydrazine and ethyl trifluoroacetoacetate is as follows (refer to Example 2):
1. ethyl 4,4,4-trifluoroacetoacetate (18.4 g, 0.1 mol) was dissolved in 12.0 g (0.2 mol) acetic acid.
2. the resulting solution was cooled to below 10 °C under stirring conditions.
3. 11.8 g (0.11 mol) of phenylhydrazine was slowly added dropwise to the above cooled solution over 0.5 hours.
4. after completion of the dropwise addition, the reaction mixture was stirred at room temperature for 1 hour, then warmed up to 80°C and continued stirring for 5 hours.
5. After completion of the reaction, the reaction solution was cooled to room temperature and diluted with 100 mL of water.
6. The precipitated solid product was collected by filtration, washed twice with 50 mL of water and finally dried using a hot air dryer.
7. 22.3 g (yield: 98.0%) of the target compound 2-phenyl-3-hydroxy-5-trifluoromethyl-2H-pyrazole was obtained as light yellow crystals.
LC-MS (EI): m/z = 228 (M+), melting point: 190-192 °C.
References
[1] Patent: EP1767528, 2007, A1. Location in patent: Page/Page column 11-12
[2] Journal of the American Chemical Society, 2018, vol. 140, # 12, p. 4259 - 4268
[3] Patent: WO2018/226828, 2018, A2. Location in patent: Paragraph 0220; 0221; 0222
[4] Patent: EP1364946, 2003, A1. Location in patent: Page/Page column 192
[5] Patent: US2005/256004, 2005, A1. Location in patent: Page/Page column 28
