A common heterocyclic compound, 141573-95-7, name is Ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate, molecular formula is C8H10F2N2O2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. 141573-95-7.
The azinium salt (10.0 g, 29.9 mmol) was suspended in 50 mL of toluene. A solution of NaOH (1.44 g, 36.0 mmol) in 50 mL of water was added and the biphasic mixture was heated to 60 C. for 3 h. The mixture was then cooled to rt, the phases split and the aqueous phase extracted with 20 mL of toluene. The combined org. phases were used in the next step without further purification. To the solution of the aminal in toluene were added ethyl alpha-ethoxymethylene-4,4-difluoro-3-oxobutyrate (6.64 g, 29.9 mmol) and p-TsOH monohydrate (0.57 g, 3.0 mmol). The solution was stirred overnight at rt, then heated to 60 C. for one hour. The solution was then cooled to it and extracted with 30 mL sat. NaHCO3 solution. The org. phase was used in the next step without further purification. To the org. phase was added 10% KOH solution (24.1 g). The biphasic mixture was heated to 60 C. and the disappearance of the ester monitored by GC. When the ester had completely vanished, the solution was cooled to rt. The phases were then split and the aqueous phase was heated to 55 C. Then, 30% H2SO4 solution (16 g) were added and stirring continued for 60 min. The solution was then cooled to 5 C. and the precipitated product removed by filtration. The precipitate was washed with cold water and dried under reduced pressure overnight (p<20 mbar, 50 C.). The product was obtained as a yellow powder (2.87 g, 16.3 mmol, 55% yield based on the azinium salt). 1H NMR (500 MHz, DMSO-d6): delta (ppm)=8.33 (s, 1H); 7.22 (t, J=54 Hz, 1H); 3.93 (s, 3H). 13C NMR (125 MHz, DMSO-d6): delta (ppm)=163.0; 145.1 (t, J=24 Hz); 136.1; 113.0 (t, J=3 Hz); 109.6 (t, J=234 Hz); 39.2. 19F NMR (470 MHz, DMSO-d6): delta (ppm)=-126.0 (d, J=54 Hz). mp=205 C. Purity (cal. HPLC): 97.1% (0.4% iso-DFP acid) The synthetic route of Ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate has been constantly updated, and we look forward to future research findings.