[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetic acid synthesis

Yield:512809-60-8 87%

Reaction Conditions:

with water;lithium hydroxide in tetrahydrofuran;methanol at 0 - 27; for 16 h;Inert atmosphere;

Steps:

Preparation of 2-(3,5-bis(difluoromethyl)-1H-pyrazol-1-yl)acetic

To a stirred solution of ethyl 2-(3,5-bis(difluoromethyl)-1H-pyrazol-1-yl)acetate (22 g, 75 mmol) in THF (50 mL) and methanol (25 mL) under N2 atmosphere at 0°C was added dropwise a solution of lithium hydroxide (5.41 g, 226 mmol) in water (25 mL). The reaction mixture was allowed to warm to 27 °C and was then stirred for 16 h at that temperature. Progress of the reaction was monitored by TLC (SiO2, 50% EtOAc/pet, Rf = 0.2, UV-active). After completion, the reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in water (100 mL) and the solution was adjusted to pH 3 using aq. HCl (2 N). The solution was extracted with EtOAc (4 X 50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and then concentrated under reduced pressure to afford 2-(3,5-bis(difluoromethyl)-1H-pyrazol-1-yl)acetic as pale-yellow solid acid, 15 g (87 %).1H NMR (400 MHz, DMSO-d6) d = 13.53 -13.24 (m, 1H), 7.46 -7.07 (m, 3H), 5.14 (s, 2H ). LCMS: (M-H) = 225.15; LCMS Purity = 98.7%.

References:

WO2020/84492,2020,A1 Location in patent:Page/Page column 46-47