Synthesis
General procedure for the synthesis of 1-methyl-3-tert-butylpyrazole-5-carboxylic acid from ethyl 3-(tert-butyl)-1-methyl-1H-pyrazole-5-carboxylate: 2 M aqueous sodium hydroxide solution (100 mL) was added to ethyl 3-(tert-butyl)-1-methyl-1H-pyrazole-5-carboxylate (185 mmol), and the reaction mixture was heated and refluxed for 2.5 hours. Upon completion of the reaction, the mixture was cooled to room temperature, diluted with 100 mL of water and the pH was adjusted to acidic (about pH 2) with 30% aqueous hydrochloric acid. The precipitated solid was collected by filtration, washed with water and dried at 60 °C for 24 h to afford 1-methyl-3-tert-butylpyrazole-5-carboxylic acid as an off-white solid (27.1 g, 80% yield). [0211] 1H NMR (400 MHz, DMSO-d6) δ: 13.19 (broad peak, 1H), 6.66 (single peak, 1H), 3.99 (single peak, 3H), 1.23 (single peak, 9H). Mass spectrum (m/z): 183 (M + H).
References
[1] Journal of Organic Chemistry, 1997, vol. 62, # 17, p. 5908 - 5919
[2] Patent: WO2009/71706, 2009, A1. Location in patent: Page/Page column 43-44
[3] Patent: US2011/218197, 2011, A1. Location in patent: Page/Page column 44
[4] Patent: US2012/202856, 2012, A1. Location in patent: Page/Page column 22
