Hydrochloric Acid → N-(5-acetylpyrazin-2-yl)-2,2-dimethylpropanamide

Participants

Reaction Conditions

Reaction Steps

A slurry of N-(5-bromo-pyrazin-2-yl)-2,2-dimethyl-propionamide (1.30 g, 5.04 mmol) and dichlorobis(triphenylphosphine)palladium(II) (35.3 mg, 0.05 mmol) in toluene (10 mL) was treated with tributyl(1-ethoxyvinyl)tin (2.00 g, 5.54 mmol). The reaction slurry was then heated under reflux, resulting in a homogeneous yellow solution. After heating under reflux for 15 h, the resulting black reaction mixture was allowed to cool to 25° C. and then was cooled to 0° C. with an ice-water bath. The cooled reaction mixture was treated slowly with a 5% aqueous hydrochloric acid solution (8.4 mL). The reaction mixture was stirred at 0° C. for 30 min and then allowed to warm to 25° C. where it was stirred for 24 h. The resulting two layers were separated, and the organic layer was further diluted with ethyl acetate (100 mL). The organic layer was then diluted with a 10% aqueous ammonium fluoride solution (100 mL), and the resulting mixture was stirred at 25° C. for 5 h. The solids were then filtered, and the filtrate layers were separated. The organic layer was washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 15% ethyl acetate/hexanes) afforded N-(5-acetyl-pyrazin-2-yl)-2,2-dimethyl-propionamide (1.07 g, 96%) as a white solid: mp 173–174° C.; (ES)+-HRMS m/e calcd for C11H15N3O2 (M+H)+ 222.1237, found 222.1240.

Provenance & Evidence