Synthesis
General procedure for the synthesis of 2-hydroxy-5-acetamidoacetophenone from 4-methoxyacetanilide and acetyl chloride: acetyl chloride (25 mL, 0.352 mol) was slowly added dropwise to a stirred suspension of 4-methoxyacetanilide (20 g, 0.121 mol) in carbon disulfide (50 mL). Anhydrous aluminum chloride (55 g, 0.412 mol) was then added in batches. The reaction mixture was heated and stirred at 80-90°C for 90 minutes. After completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was carefully poured into a mixture of crushed ice and water. The precipitated solid was collected by filtration and washed well with water. The crude product was dissolved in 5% (w/v) aqueous sodium hydroxide solution and the solution was filtered through Celite. The filtrate was acidified to pH 1 with concentrated hydrochloric acid to precipitate 2-hydroxy-5-acetamidoacetophenone. The product was collected by filtration, washed with water and dried to give a white solid (21.05 g, 90% yield): melting point 162-164°C; IR (KBr)ν: 3452 cm-1 (O-H stretching vibration), 1657 cm-1 (C=O stretching vibration); 1H NMR (DMSO-d6, 500 MHz): δ 2.02 (s, 3H, - NHCOCH3), 2.58 (s, 3H, -COCH3), 6.90 (d, 1H, 5-H), 7.65 (dd, 1H, 6-H), 8.06 (s, 1H, 2-H), 9.89 (s, 1H, -NHCOCH3), 11.54 (s, 1H, -OH). Elemental analysis (C10H11NO3) calculated values: C, 62.17; H, 5.74; N, 7.25. measured values: C, 62.35; H, 5.82; N, 7.19.
References
[1] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 13, p. 3919 - 3928
[2] Patent: WO2012/107262, 2012, A1. Location in patent: Page/Page column 29
[3] Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4324 - 4330
[4] Journal of Medicinal Chemistry, 1992, vol. 35, # 21, p. 3973 - 3976
[5] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 9, p. 2079 - 2098
