90357-51-0

N-[4-Cyano-3-(trifluoromethyl)phenyl]-2-methyl-2-oxiranecarboxamide, is an intermediate in synthesis of more complex pharmaceutical compounds. It is used in the synthesis of potential impurities of Bicalutamide (B382000), which is an oral nonsteroidal, anti-androgen drug used for prostate cancer.

General procedure for the synthesis of N-[4-cyano-3-(trifluoromethyl)phenyl]methoxyacrylamide from N-(4-cyano-3-(trifluoromethyl)phenyl)methoxyacrylamide: N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methacrylamide (50.8 g, 0.2 mol) and phthalic anhydride (47.3 g, 0.32 mol) were dissolved in 350 ml of 1,2-dichloroethane. 50% hydrogen peroxide (23.1 g, 0.34 mol) was added slowly and dropwise at 35?40 °C. The progress of the reaction was monitored by HPLC until the content of the feedstock N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methylacrylamide decreased to less than 0.5% and the reaction was completed. Subsequently, 1,2-dichloroethane was removed by distillation to give the crude product. To the crude product, 300 g of water was added and neutralized by adding 26 g of sodium carbonate. Next, 13 g of sodium sulfate was added and filtered after stirring for 0.5 hours. The filter cake was washed with 50 g of water and dried to give the final product N-[4-cyano-3-(trifluoromethyl)phenyl]-2,3-epoxy-2-methylpropanamide 49 g in 90.7% yield.

[1] Journal of Organic Chemistry, 2003, vol. 68, # 26, p. 10181 - 10182
[2] Patent: CN106905265, 2017, A. Location in patent: Paragraph 0015
[3] Journal of Medicinal Chemistry, 2007, vol. 50, # 5, p. 1028 - 1040
[4] Journal of Organometallic Chemistry, 2011, vol. 696, # 5, p. 1049 - 1056
[5] European Journal of Medicinal Chemistry, 2016, vol. 118, p. 230 - 243