Acetic Anhydride → tert-Butyl 5-iodo-1H-indazole-1-carboxylate

Participants

Reaction Steps

To an ice bath cooled solution of 4-iodo-2-methylaniline (20 g, 83.24 mmol) in chloroform (250 mL) was added dropwise a solution of acetic anhydride (21.2 g, 208.11 mmol) in chloroform (50 mL). Upon completion of the addition, the mixture was stirred at room temperature for 1 hour. Potassium acetate (2.5 g, 24.97 mmol) and isoamylnitrite (22.3 mL, 166.48 mmol) were added and the mixture was heated at 70° C. for 20 hours. The mixture was cooled and quenched with saturated aqueous NaHCO3 to pH 7. The mixture was extracted with dichloromethane, and the organics were dried over sodium sulfate and filtered. The solvent was evaporated under reduced pressure. The crude solid was washed with methanol, dissolved in tetrahydrofuran (200 mL) and treated with a warm solution of KOH (60 g) in water (200 mL). The mixture was stirred for 15 minutes and was treated with 6 N HCl to pH 1. The layers were separated, the organic layer was dried over sodium sulfate and filtered, and the solvent was evaporated under reduced pressure. The crude solid was dissolved in dichloromethane (500 mL) and triethylamine (23 mL, 166.48 mmol), and di-tert-butyldicarbonate (23.6 g, 108.2 mmol) and a catalytic amount of dimethylaminopyridine (˜5 mg) were added. The mixture was stirred at room temperature for 2 hours, diluted with water, extracted with dichloromethane, and dried with sodium sulfate and filtered. The solvent was evaporated under reduced pressure to afford the title compound. MS (ESI+) m/z 344.9 (M+H)+.

Provenance & Evidence