Hydrochloric Acid → N-cyclopentyl-N,2-dihydroxy-4-methoxybenzamide

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Reaction Steps

Pyridine (2.05 mL, 25 mmol) and acetyl chloride (0.89 mL, 12.5 mmol were added to a solution of 4-methoxy salicylic acid (0.84 g, 5 mmol) in CH2Cl2 (20 mL) at 0° C. The reaction mixture was gradually warmed to room temperature over 30 min and then poured into water. The resulting biphasic mixture was further stirred for 1 h and then acidified with 1 N HCl and extracted with ethyl acetate. The crude acetoxy compound (assuming 100% conversion) obtained was then converted to the acid chloride by heating to reflux with oxalyl chloride (1.3 mL, 15 mmol) in CH2Cl2 (20 mL) for 1 h. After removal of the volatile materials, the acid chloride (1.05 g, 4.38 mmol) in CH2Cl2 (20 mL) was added to a stirred mixture of sodium carbonate (1N, 17.5 mL) and C5H9NH.OH (1.32 g, 13.2 mmol) in tetrahydrofuran (30 mL) at 0° C. The resulting mixture was stirred at room temperature for 1 h and then acidified with 0.5 M HCl and then extracted with ethyl acetate. The crude product was purified by column chromatography on silica using hexanes:ethyl acetate to afford N-cyclopentyl-N,2-dihydroxy-4-methoxybenzamide (1 g, 79%) as a colorless solid. 1H NMR (300 MHz, DMSO-d6): δ 7.88 (d, 1H, J=8.6 Hz), 6.92 (d, 1H, J=8.6 Hz), 6.82 (s, 1H), 3.80 (s, 3H), 3.79-3.70 (m, 1H), 1.69-1.63 (m, 2H), 1.55-1.52 (m, 6H). LC-MS (ESI) Calcd for C13H17NO4 [M+H]+: 252.12. Found: 252.00.

Provenance & Evidence