Reaction Steps
To a mixture of 3,5-bis(trifluoromethyl)phenylisothiocyanate (2.83 g, 10.4 mmol), DCM (20 mL) and tert-butyl cyanoacetate (1.65 mL, 11.6 mmol) DBU (4.0 mL, 26.8 mmol) was added, whereby an exothermic reaction occurred. The resulting mixture was stirred at room temperature for 2 h, and then magnesium sulfate (2.0 g), isoamylamine (2.35 mL) and mercury(II) oxide (6.80 g, 31.4 mmol) were added. After stirring for 25 h, the mixture was mixed with celite, filtered, and the filtrate was mixed with 0.5 M hydrochloric acid. After an additional filtration the filtrate was extracted (3×100 mL DCM), the combined extracts were washed with brine (2×300 mL, emulgates strongly), dried (magnesium sulfate) and concentrated. Column chromatography (80 g silica gel, gradient elution with heptane/ethyl acetate 10:0 to 2:3) gave 2.23 g (39%) of the title compound as a colourless solid, along with 0.72 g (15%) of 3-[3,5-bis(trifluoromethyl)phenylamino]-2-cyano-3-(3-methylbutylamino)acrylic acid tert-butyl ester. A sample of the title compound was further purified by recrystallization. Colourless solid, mp. 167-168° C. (ethyl acetate). LCMS: elution at 15.4 min, MH+ : 549; 1H NMR (400 MHz, DMSO-d6): δ=1.40 (s, 9H), 1.43 (m, 4H), 1.57 (m, 2H), 1.71 (q, J=7 Hz, 2H), 2.35 (m, 2H), 3.20 (q, J=7 Hz, 2H), 3.31 (m, 2H), 7.66 (s, 2H), 7.68 (s, 1H), 8.95 (s, br, 1H), 9.52 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ=22.93, 27.93, 28.11, 28.32, 29.23, 36.44, 41.55, 44.47, 48.38, 61.93, 79.66, 115.36, 118.75, 119.89, 123.18 (q, J=275 Hz), 131.02 (q, J=33 Hz), 142.33, 160.59, 167.95, 174.74. Anal. Calcd. for C25H30F6N4O3 (548.53): C, 54.74; H, 5.51; N, 10.21. Found: C, 54.62; H, 5.66; N, 9.97.
