Sodium Hydroxide → 5-(Trifluoromethyl)pyrazin-2-amine

Participants

Reaction Steps

To an ice bath-cooled solution of 5,6-diaminopyrimidin-4-ol (18 g, 143 mmol) in 3M sodium hydroxide (180 mL, 540 mmol), was added 3,3-dibromo-1,1,1-trifluoropropan-2-one (25.2 g, 93 mmol). The reaction was stirred for 3 days at ambient temperature. The solids were filtered, dissolved in 60% sulfuric acid (140 mL), and stirred at 135° C. for 8 h. The reaction was cooled, poured over ice and allowed to sit for 16 hours. The solution was neutralized to pH 8 with conc. ammonium hydroxide and extracted with ethyl acetate (5×100 mL), dried over sodium sulfate, filtered and concentrated. The solid residue was recrystallized from benzene/hexane to afford 5-(trifluoromethyl)pyrazin-2-amine (2.28 g, 14 mmol, 15% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.32 (1H, s), 7.99 (1H, d, J=1.26 Hz), 5.02 (2H, br. s.). MS (LC/MS) R.T.=1.56; [M+H]+=164.03.

Provenance & Evidence