Uses
Ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutyrate may be employed as a starting reagent for the synthesis of 1-methyl-3-trifluoromethyl-1
H-pyrazole-4- carboxylic acid.
General Description
Ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutyrate has been reported to participate in the microwave-assisted synthesis of ethyl 1-[4-(2,3,3-trichloroacrylamido)phenyl]-5-(trifluoromethyl)-1
H-pyrazole-4-carboxylate.
Synthesis
General procedure for the synthesis of ethyl ethoxy-2-methylene trifluoroacetoacetate from triethyl orthoformate and ethyl trifluoroacetoacetate: ethyl 4,4,4-trifluoro-3-oxobutanoate (30 g, 162.9 mmol) was added to a solution of acetic anhydride (50 mL) containing triethoxymethane (72.4 g, 488.8 mmol). The reaction mixture was stirred continuously at 135 °C for 18 hours. Upon completion of the reaction, the brown mixture was concentrated to afford ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoate (38 g, 97.1% yield), the product was a brown oil that could be used in subsequent reactions without further purification. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 1.23-1.33 (m, 3H), 1.40 (dt, J = 14.18, 7.19 Hz, 3H), 4.19-4.36 (m, 4H), 7.66-7.87 (m, 1H).
References
[1] Journal of medicinal chemistry, 2000, vol. 43, # 21, p. 3995 - 4004
[2] Patent: US2018/170909, 2018, A1. Location in patent: Paragraph 0824; 0825
[3] Patent: CN106432183, 2017, A. Location in patent: Paragraph 0031; 0032
[4] Patent: WO2016/151403, 2016, A1. Location in patent: Paragraph 00520
[5] Journal of Molecular Structure, 2018, vol. 1171, p. 631 - 638
