p-Toluenesulfonic acid → HCID 21834433, compound

Participants

Reaction Steps

Methyl 5-(4-methyl-6-(2,5-dimethylpyrrol-1-yl)-2-pyridinyl)pentanoate (330 mg, 1.10 mmol) was dissolved in 6.0 mL of 95% ethanol, and 1.0 mL of water was added followed by 199 mg (3.08 mmol) of 87% potassium hydroxide. After 2 h, an additional 1 mL of water was added along with 351 mg (5.06 mmol) of hydroxylamine hydrochloride. The solution was heated to reflux for 20 h, then cooled and concentrated. The residue was dissolved in 15 mL of 2 N aqueous hydrochloric acid and washed with 2×10 mL of ethyl ether. The aqueous layer was evaporated and triturated with 3×5 mL of methanol. The methanol extracts were evaporated to give 619 mg of partially crystalline material. A portion (495 mg) of this material was dissolved in 6.0 mL of methanol along with 510 mg (2.68 mmol) of p-toluenesulfonic acid and heated to reflux for 20 h. The reaction was cooled and concentrated and the residue was partitioned between 25 mL of saturated aqueous sodium bicarbonate and 50 mL of ethyl acetate. The aqueous layer was extracted with 2×25 mL of ethyl acetate. The combined organic layers were washed with 50 mL of saturated aqueous sodium chloride, dried (sodium sulfate), decanted, and evaporated. The residue was purified by flash column chromatography on 20 g of silica gel, eluting with 500 mL of 50% ethyl acetate in dichloromethane to give 119 mg (61% yield) of methyl 5-(6-amino-4-methyl-2-pyridinyl)pentanoate as an amber oil.

Provenance & Evidence