5-Chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid synthesis

Yield:-

Reaction Conditions:

Stage #1:5-chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehyde with dihydrogen peroxide;sodium hydroxide in water;toluene at 37 - 50; for 7 h;
Stage #2: with hydrogenchloride in water; pH=2

Steps:

IIb-1 Synthesis of 5-chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (example IIb-1)
In a 500 ml flask, 6.0 g (31 mmol) of 5-chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehyde were added to 30 ml of toluene. A solution of 2.4 g (62 mmol) of sodium hydroxide in 6ml of water was added to the reaction mixture, followed by 103 ml of a 30% solution of hydrogen peroxide in water, whilst keeping the temperature below 37°C. After the end of the addition, the reaction mixture is stirred at 50°C for 7 hours. Once the reaction mixture is back to room temperature, the two phases are separated and the organic phase is extracted with 100 ml of water. The combined aqueous phases are acidified to pH 2 with aqueous hydrochloric acid. The resulting white precipitate is filtered, washed with 2*20 ml of water, and dried to yield 3.2 g of 5-chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid as a white solid ¹H NMR (400 MHz, DMSO-d₆) δ ppm : 13.19 (s, 1H); 7.12 (t, 1H, J_HF= 53.60 Hz); 3.78 (s, 3H) IR (KBr) : 1688 cm^-1 (C=O); 2200-3200 cm^-1 broad (hydrogen bond)

References:

Bayer CropScience AG EP2251331, 2010, A1 Location in patent:Page/Page column 24

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