Hydrochloric Acid → 6-chloro-1H-indazole

Participants

Reaction Conditions

Reaction Steps

A slurry of 5-chloro-2-methylaniline (1-1, 30 g, 0.21 mol) in water (200 mL) was treated with HCl (12N, 53 mL, 0.64 mol). The resulting solution was cooled to 0° C. and reacted with aqueous solution of sodium nitrite (14.6 g, 0.21 mol). After 30 min. stirring, any insoluble particles were removed by filtration and the filtrate solution was treated at 0° C. with sodium tetrafluoroborate dissolved in water (150 mL). Precipitates so formed was collected by filtration, washed with ice-cold water, cold methanol and then with ethylether. The product (1-2) was dried in vacuo and then suspended in chloroform (500 mL) in the presence of potassium acetate (34 g, 0.35 mol) and 18-crown-6 (2.29 g, 8.67 mmol). The reaction mixture was stirred at the ambient temperature for 1.5 h, partitioned between ethyl acetate and water. The organic layer was washed with brine, separated, dried (MgSO4) and concentrated in vacuo. Trituation with dichloromethane and hexanes afforded the desired product as an orange powder (1-3); 1H NMR (400 MHz, DMSO-d6) δ 13.18 (bs, 1H), 8.11 (s, 1H), 7.79 (d, 1H, J=8.7 Hz), 7.62 (s, 1H), 7.13 (dd, 1H, J=7.9, 1.9 Hz).

Provenance & Evidence