Acetic Anhydride → 5-(3-chlorophenoxy)-1H-indazole

Participants

Reaction Conditions

Reaction Steps

4-(3-Chloro-phenoxy)-2-methyl-phenylamine (0.87 g, 3.74 mmol) was dissolved in chloroform. Ac2O (0.878 g, 8.61 mmol) was then added dropwise over 10 min at 0° C. and the mixture was stirred for 1 h at 25° C. Potassium acetate (110 mg, 1.12 mmol) and t-butyl nitrite (829 mg, 8.05 mmol) were added to the reaction mixture and the mixture was heated at 80° C. for 16 h. This mixture was then concentrated, conc. HBr was added and the mixture was stirred for 16 h at 25° C. The pH of the mixture was adjusted to pH 7 using KOH solution and the resulting mixture was extracted with EtOAc (3×50 mL). The organic phase was washed with brine (3×10 mL), dried over sodium sulfate and concentrated. The residue was purified by column chromatography (11% EtOAc in hexanes) to afford 5-(3-chloro-phenoxy)-1H-indazole (152 mg, 17%). MS (M+H)+=245; 1H NMR (CDCl3) δ: 8.03 (s, 1H), 7.50 (d, J=8.7 Hz, 1H), 7.37 (br.s., 1H), 7.21 (d, J=6.18 Hz, 1H), 7.16 (dd, J=6.5, 1.1 Hz, 1H); 7.08 (d, J=5.8 Hz, 1H), 6.93 (br.s., 1H), 6.86 (d, J=6.0 Hz, 1H).

Provenance & Evidence