p-Toluenesulfonic acid → HCID 53949251, compound

Participants

Reaction Steps

To a solution of diethyl (2-(4-methyl-6-(2,5-dimethylpyrrol-1-yl)-2-pyridinyl)ethyl)malonate (96 mg, 0.26 mmol) in 1.4 mL of ethanol was added 0.3 mL of water, followed by 105 mg of 87% potassium hydroxide (1.63 mmol). After the mixture had been stirred at room temperature for 7 h., additional water (0.3 mL) was added along with 166 mg (2.39 mmol) of hydroxylamine hydrochloride. The mixture was refluxed 12 h. After removing solvent in vacuo, the residue was dissolved into 10 mL of 2.0 N aqueous hydrochloric acid and washed with 2×10 mL of diethyl ether. The aqueous phase was concentrated and swirled with 3×1 mL of methanol. The methanol extracts were combined, filtered, and evaporated. The residue was dissolved in 5.0 mL of methanol along with 149 mg (0.78 mmol) of p-toluenesulfonic acid and heated to reflux for 16 h. The reaction was cooled and concentrated and the residue was partitioned between 15 mL of saturated aqueous sodium bicarbonate and 30 mL of ethyl acetate. The organic layer was washed with 15 mL of saturated aqueous sodium chloride, dried (sodium sulfate), decanted, and evaporated. The residue was purified by flash column chromatography on 10 g of silica gel, eluting with 200 mL of 40% ethyl acetate in dichloromethane and 200 ML of 50% ethyl acetate in dichloromethane to give 36 mg (52% yield) of dimethyl (2-(6-amino-4-methyl-2-pyridinyl)ethyl)malonate.

Provenance & Evidence