反应详情

温度

75 °C

To a suspension of sodium selenide (4.6 g, 37.5 mmol) in DMF (37 mL) was added a solution of 2-[bis(methylsulfanyl)methylene]malononitrile (6.37 g, 37.5 mmol; Baraldi, P. G.; Fruttarolo, F.; Tabrizi, M. A.; Preti, D.; Romagnoli, R.; El-Kashef, H.; Moorman, A.; Varani, K.; Gessi, S.; Merighi, S.; Borea, P. A. J. Med. Chem., 2003, 46, 1229-1241; Thomae, D.; Perspicace, E.; Henryon, D.; Xu, Z.; Schneider, S.; Hesse, S.; Kirsch, G.; Seck, P. Tetrahedron, 2009, 65, 10453-10458) in DMF (18 mL) at rt for 5 min and stirred the mixture at 70-80° C. for 2 h. Then ethyl chloroacetate (6.38 mL, 75 mmol) was added dropwise to the reaction mixture and again stirred at 70-80° C. for 2 h. Then, a suspension of sodium methoxide (2.0 g, 37.5 mmol) in methanol (37 mL) was added and stirring was continued for 1.5 h at the same temperature. The mixture was allowed to rt and poured into cold water and stirred for 15 min. The solution was extracted with chloroform (3×100 mL). The combined organic layer was washed with water, brine and dried over sodium sulfate. The solution was filtered and evaporated the solvent. The residue was chromatographed over silica gel column using hexane-ethyl acetate (90:10) as eluents to give the product as a brown color solid (2.2 g, 21%), mp 128-130° C. 1H NMR (400 MHz, CDCl3): δ 5.86 (2H, br s), 4.27 (2H, q, J=7.06 Hz), 2.67 (3H, s), 1.32 (3H, t, J=7.0 Hz); LC-MS (positive ion mode): m/z 289, 291 (M+H)+.

1. stirringagain stirred at 70-80° C. for 2 h
2. additionwas added
3. stirringstirring
4. waitwas continued for 1.5 h at the same temperature
5. customwas allowed to rt
6. stirringstirred for 15 min
7. extractionThe solution was extracted with chloroform (3×100 mL)
8. washThe combined organic layer was washed with water, brine
9. dry with materialdried over sodium sulfate
10. filtrationThe solution was filtered
11. customevaporated the solvent
12. customThe residue was chromatographed over silica gel column