Methylhydrazine → Ethyl 3-difluoromethyl-1-methyl-4-pyrazole carboxylate

Participants

Reaction Conditions

Reaction Steps

40% Methylhydrazine (565 g, 4.91 moles) in aqueous solution and K2CO3 (237 g, 1.72 moles) are dissolved in water (2134 g) and mixed to make a clear solution. Toluene (2292 g) is added to make a two phase system, and then cooled to −10-0° C. Crude ethyl 2-ethoxymethylenedifluoroacetoacetate (Formula VI) (˜1010 g, ˜4.91 moles) in toluene (1500 g) is then added dropwise with effective agitation while maintaining at the same temperature. The agitation is kept constant for 1-2 hours until GC shows the content of ethyl 2-ethoxymethylenedifluoroacetoacetate <0.2%. Two phases are separated and the organic phase is concentrated until GC shows toluene content <5%. A mixture of toluene (757 g) and petroleum ether (3028 g) (bp. 60-90° C.) is added in and then heated up to 50-60° C. to make a solution. The yellowish solid precipitated after the solution is slowly cooled down to 10-15° C. The solid is collected by filtration and dried in a vacuum oven to give a yellowish solid (828 g, Yield=82.5%). The product only contains 0.01% of the positional isomer of formula XI and 0.01% of the des-difluoro-impurity of Formula XII.

Provenance & Evidence