BUTTPARK 114\40-88 synthesis

Yield:28313-73-7 78 %

Reaction Conditions:

Stage #1: 3-trifluoromethylanilinewith hydrogenchloride;sodium nitrite in water;
Stage #2: ethyl 2-cyanoacetatewith sodium acetate in ethanol;water;Cooling with ice;

Steps:

Ethyl 2-cyano-2-(2-(3-trifluoromethyl)phenylhydrazono)acetate (3)

To an ice-cooled solution of m-trifluoromethylaniline 1(1.61 g, 0.01 mol) in hydrochloric acid (2.5 mL) and distilledwater (5 mL), a solution of sodium nitrite (0.69 g,0.013 mol) in distilled water (5 mL) was added. The colddiazotized solution was then added portion-wise to a wellstirredcold solution of ethyl cyanoacetate (1.13 mL, 0.01 mol), in 50% aqueous ethanol (10 mL) containing sodiumacetate (0.9 g, 0.01 mol). The reaction mixture was kept onice for 8 h. and then filtered and the obtained solid was driedand crystallized from ethanol.Yield: 78% as yellow crystals; m.p.: 119-121 °C; IR: ν/cm-1: 3218 (NH), 3081 (CH-aromatic), 2986 (CH-aliphatic),2219 (C≡N), 1741 (C=O), 1603 (C=N), 1564 (N=N);1H NMR (400 MHz, DMSO-d6) δ/ppm: 1.26 (t, 3H,CH2CH3), 4.26 (q, 2H, CH2CH3), 7.47 (d, 1H, J = 9 Hz, Ar-H), 7.61 (t, 1H, Ar-H), 7.71 (d, 1H, J = 9 Hz, Ar-H), 7.76(s, 1H, Ar-H), 12.38 (s,1H, NH exchangeable by D2O).

References:

Fayed, Eman A.;Gohar, Nirvana A.;Bayoumi, Ashraf H.;Ammar, Yousry A. [Medicinal Chemistry Research,2023,vol. 32,# 2,p. 369 - 388]