文档介绍：3-二氟甲基-1-甲基-1H-吡唑-4-甲酸的合成 2
1. Synthesis of Ethyl 4,4-difluoro-3-oxobutyrate 1
g of sodium hydride Were added to 300 ml of absolute tetrahydrofuran. At 35-400 C., a solution of 62g of ethyl difluoroacetate in 44 g of ethyl acetate Was added. After 7 h of stirring at 40℃., the reaction mixture Was stirred into 1 I of ice-Water, the pH Was adjusted to 3 using 10% strength sulfuric acid and the mixture Was extracted tWice With in each case 300 ml of methyl tert-butyl ether. anic phase Was Washed tWice With brine, dried over sodium sulfate and concentrated under reduced pressure. The residue Was distilled. This gave g of the product as a colorless oil
2. Ethyl 2-ethoxymethylene-4,4-dif luoro-3-oxobutyrate 2
A mixture of 30 g of ethyl 4,4-difluoro-3-oxobutyrate 1, 44g of triethyl ortho-formate and 55g of acetic anhydride Was stirred under reflux for 4 h and then distilled. This gave 35g of the product as a colorless oil. Bp=85-87℃.
of Ethyl 3-difluoromethyl-1-meth ylpyrazole-4-carboxylate At -40℃., g of ethyl 2-ethoxymethylene-4, 4-difluoro-3-oxobutyrate 2 Were dissolved in 250 ml of of methylhydraZine Were added and the mixture Was stirred at 40℃. for 1 h and at room temperature for 15 h. The reaction mixture Was concentrated under reduced pressure. The residue Was recrystallized from pentane. This gave g ofthe product. .: