1H-Pyrazole-3-carboxylic acid, 4-bromo-1-(1,1-dimethylethyl)- synthesis

Yield:682757-51-3 89%

Reaction Conditions:

with sulfuric acid at 100; for 2 h;

Steps:

24.1 Step 1: 4-bromo-1-tert-butyl-1H-pyrazole-3-carboxylic-acid

Concentrated sulfuric acid (0.24 mL, 4.3 mmol) was added to a suspension of 4-bromo-1H-pyrazole-3-carboxylic-acid (860 mg, 4.3 mmol) in t-BuOH (2.1 mL, 22 mmol). The reaction mixture was stirred at 100° C. for 2 h. Most of the solvent evaporated during the heating and a white solid remained in the flask. After cooling to room temperature, the pH was adjusted to 4 by adding saturated aq. NaHCO₃. The aqueous layer was extracted with ethyl acetate (2×40 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO₄, filtered and concentrated under reduced pressure to afford 4-bromo-1-tert-butyl-1H-pyrazole-3-carboxylic-acid (1.0 g, 89%) as a white solid. ¹H NMR (300 MHz, DMSO) δ 1.52 (s, 9H), 8.23 (s, 1H), 12.92 (br s, 1H).

References:

US2016/95858,2016,A1 Location in patent:Paragraph 2660; 2661