反应详情

温度

95 °C

To a solution of 1-(2-chloro-5-(4-morpholinylmethyl)-3-thienyl)ethanone (Preparation 63, 9.53g) in dimethylcarbonate (200 mL) is added NaH (1.53 g; 60% dispersion in mineral oil) portionwise at ambient temperature. The reaction mixture is heated to 95° C. for 3 h. The reaction vessel is cooled to ambient temperature and the mixture is poured into ice cold water (500 mL) containing acetic acid (15 mL). The aqueous layer is extracted with Et2O (3×100 mL). The organic layer is separated, dried over MgSO4, filtered, and concentrated in vacuo. The crude brown liquid is purified by silica gel column chromatography (4/1, hexanes/EtOAc) to afford 4.77g (41%) of the title compound as a tan solid. Physical characteristics: m.p. 67-68° C.; 1H NMR (300 MHz, CDCl3) δ 7.21, 3.99, 3.78, 3.71, 3.60, 2.50; IR (diffuse reflectance) 2822, 1738, 1663, 1461, 1399, 1350, 1336, 1316, 1286, 1265, 1156, 1113, 1009, 1004, 864 cm−1; MS (ESI+) m/z 318; Anal. Found: C, 48.89; H, 5.13; N, 4.45.

1. temperatureThe reaction vessel is cooled to ambient temperature
2. extractionThe aqueous layer is extracted with Et2O (3×100 mL)
3. customThe organic layer is separated
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe crude brown liquid is purified by silica gel column chromatography (4/1, hexanes/EtOAc)