tert-Butyl mercaptan → 7-Bromo-5-chloro-1H-indazole

Participants

Reaction Conditions

Reaction Steps

2-Bromo-4-chloro-6-methylaniline (13.2 g, 59.90 mmol) was suspended in 24% hydrochloric acid (40 mL). The stirred mixture was cooled to 0° C. and treated with sodium nitrite (4.54 g, 65.90 mmol) in water (10 mL), dropwise over 30 min. The mixture was then buffered to ca. pH 5 with sodium acetate. This mixture was kept at 0° C. and added in portions to a stirred solution of 2-methyl-2-propanethiol (6.8 mL, 59.9 mmol) in ethanol (40 mL) at 0° C. over 30 min. After the addition, the mixture was stirred at 0° C. for 30 min then transferred to crushed ice, and extracted with ethyl acetate (2×). The organics were pooled together, washed with brine (2×), dried over sodium sulfate, filtered, and concentrated. The resulting residue was dissolved in dimethyl sulfoxide (50 mL) and transferred to a solution of potassium tert-butoxide (53.7 g, 479 mmol) in dimethyl sulfoxide (200 mL) at 0° C. via cannula. The ice-bath was removed and stirring continued for 30 min. The reaction was then poured into a mixture of crushed ice (400 mL) and 10% hydrochloric acid (200 mL) to give a precipitate which was collected by filtration. The resulting solid was triturated with hexanes to afford 7.5 g (54%) as a brown powder. 1H-NMR (CDCl3, 300 MHz) δ 7.97 (s, 1H), 7.60 (s, 1H), 7.44 (s, 1H). Mass spec.: 232.90 (MH)+.

Provenance & Evidence