1H-1,2,4-Triazole → 2-Methoxy-4-(1H-1,2,4-triazol-1-yl)aniline

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-bromo-2-methoxyaniline (208 mg, 1.03 mmol), 1,2,4-triazole (80 mg, 1.13 mmol), Cs2CO3 (0.67 g, 2.06 mmol) and CuI (20 mg, 0.103 mmol) in DMF was heated at 110° C. for 20 h. Further portions of 1,2,4-triazole (0.1 g, 1.44 mmol), Cs2CO3 (0.67 g, 2.06 mmol) and CuI (0.1 g, 0.52 mmol) were added and the mixture was heated a further 72 h at 110° C. The mixture was cooled, diluted with ethyl acetate (20 mL) and washed with water (2×20 mL). The combined aqueous washes were re-extracted with ethyl acetate (20 mL). The combined organics were passed through a phase separation cartridge and the solvent removed under reduced pressure. Purification of the residue via silica gel column chromatography (0-100% ethyl acetate/isohexane) gave 2-methoxy-4-(1H-1,2,4-triazol-1-yl)aniline as a light red solid (92 mg, 47%). 1H NMR (400 MHz, CDCl3): δ 8.41 (s, 1H); 8.05 (s, 1H); 7.11 (d, J=2.3, 1H); 6.99 (dd, J=8.3, 2.3, 1H); 6.74 (d, J=8.3, 1H); 3.97 (s, 2H); 3.92 (s, 3H).

Provenance & Evidence