Tetrahydrofuran → 2-Amino-3-benzyl-5-bromo-6-chloropyrazine

Participants

Reaction Steps

Under an argon atmosphere, to anhydrous THF (40 mL) was added zinc chloride (1.0 M in diethyl ether) (23.7 mL, 23.7 mmol), and to the mixture was added benzyl magnesium chloride (2.0 M in THF) (10.4 mL, 20.8 mmol). After stirring at room temperature for 30 minutes, to the mixture were successively added dichlorobis(triphenylphosphine)palladium(II) (488 mg, 695 μmol) and 2-amino-3,5-dibromo-6-chloropyrazine (4) (4.00 g, 13.9 mmol) at room temperature. The mixture was stirred overnight (15 hours and a half) at room temperature as it was. After to the mixture was added water, the product was extracted with ethyl acetate (×3). The combined organic extract was washed successively with water (×1) and brine (×1), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=5/1) to give 2-amino-3-benzyl-5-bromo-6-chloropyrazine (5) (3.64 g, 12.2 mmol, 87.6%) as a yellow solid. TLC Rf=0.25 (n-hexane/ethyl acetate=4/1); 1H NMR (500 MHz, CDCl3) δ 4.08 (s, 2H), 4.50 (s, 2H), 7.19-7.24 (m, 2H), 7.27-7.37 (m, 3H); 13C NMR (126 MHz, CDCl3) δ 40.1, 123.8, 127.5, 128.4, 129.3, 135.3, 139.5, 144.9, 151.3.

Provenance & Evidence