Chloroacetyl chloride → 2-chloro-N-(1H-indazol-5-yl)acetamide

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Reaction Steps

Chloroacetyl chloride (3.14 ml, 39.4 mmol) was added to a solution of 5-aminoindazole (5.0 g, 37.5 mmol) in tetrahydrofuran (100 ml) at room temperature, followed by adding thereto a solution of triethylamine (5.76 ml, 41.3 mmol) in tetrahydrofuran (30 ml) at 0° C., and the resulting mixture was stirred at 0° C. for 30 minutes. Subsequently, a saturated aqueous sodium carbonate solution and then water were added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was suspended in ethanol and stirred, followed by filtration. To a solution of the solid collected by the filtration and dissolved in a mixture of tetrahydrofuran (25 ml) and methanol (25 ml) was added a 2N-aqueous lithium hydroxide solution (9.3 ml) at 0° C., and stirred at room temperature for 30 minutes. Then, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 2-chloro-N-(1H-indazol-5-yl)acetamide (1.90 g, 46%).

Provenance & Evidence