Potassium Carbonate → N-[1-(6-Hydroxy-benzofuran-3-ylmethyl)-piperidin-4-yl]-acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-acetamidopiperidine (429 mg, 3.00 mmol) and K2CO3 (1.14 g, 8.25 mmol) in MeCN (5 mL) was added a solution of acetic acid 3-chloromethyl-benzofuran-6-yl ester (450 mg, 2.0 mmol) in MeCN (5 mL). The reaction mixture was further diluted with MeCN (10 mL) and heated (50° C., 15 h). The solvent was removed in vacuo and the remaining residue was suspended in 5-10% CH3OH in water and enough concentrated acetic acid was added until all solids were dissolved (pH ˜7-8). The solution was slowly basified using 4 N KOH until precipitate was observed. The precipitate was filtered and rinsed with water. The pH of the mother liquor was further adjusted (4 N KOH and concentrated acetic acid) to produce additional precipitate, which was filtered and rinsed with water. This process of pH adjustment and solid filtration was repeated until no additional precipitate was observed. The precipitate was combined and dried in vacuo to provide the title compound as an off white solid (419 mg, 73%). MS (ESI): mass calcd. for C16H20N2O3, 288.15; m/z found, 289.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 9.44 (s, 1H), 7.69 (d, J=7.6, 1H), 7.63 (s, 1H), 7.47 (d, J=8.4, 1H), 6.86 (d, J=2.0, 1H), 6.72 (dd, J=8.4, 2.1, 1H), 3.56-3.44 (m, 3H), 2.86-2.74 (m, 2H), 1.99 (t, J=10.6, 2H), 1.76 (s, 3H), 1.74-1.62 (m, 2H), 1.43-1.27 (m, 2H).

Provenance & Evidence