Reacción #1617015

Ecuación de reacción

sodium methoxide

Borea

ethyl chloroacetate

DMF

sodium selenide

DMF

2-[bis(methylsulfanyl)methylene]malononitrile

→

solid

Rendimiento 21.0%

Ethyl 3-amino-4-cyano-5-methylthioselenophene-2-carboxylate

Rendimiento 21.0%

Disolventes

methanol

water

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGagain stirred at 70-80° C. for 2 h
2. 2
   workup.ADDITIONwas added
3. 3
   workup.STIRRINGstirring
4. 4
   workup.WAITwas continued for 1.5 h at the same temperature
5. 5
   Otrowas allowed to rt
6. 6
   workup.STIRRINGstirred for 15 min
7. 7
   ExtracciónThe solution was extracted with chloroform (3×100 mL)
8. 8
   LavadoThe combined organic layer was washed with water, brine
9. 9
   Secadodried over sodium sulfate
10. 10
    FiltraciónThe solution was filtered
11. 11
    Otroevaporated the solvent
12. 12
    OtroThe residue was chromatographed over silica gel column

Procedimiento

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)+.

Fuente