Reacción #45075

Ecuación de reacción

ethyl 5-bromothiophene-2-carboxylate

1,2-dimethyl-piperazine

rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl

cesium carbonate

→

ethyl 5-(3,4-dimethylpiperazin-1-yl)thiophene-2-carboxylate

Rendimiento 47.7%

Disolventes

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe crude product was purified by ion exchange chromatography
2. 2
   workup.DISSOLUTIONThe crude material was dissolved in methanol
3. 3
   LavadoThe desired product was eluted from the column
4. 4
   Otrowere evaporated to dryness
5. 5
   Otroto afford the crude product as a brown oil
6. 6
   OtroThis material was further purified by silica column chromatography
7. 7
   Lavadoeluting with a gradient of 1 to 5% MeOH in DCM
8. 8
   OtroPure fractions were evaporated to dryness

Procedimiento

Palladium(II) acetate (0.112 g, 0.50 mmol) was added to a mixture of ethyl 5-bromothiophene-2-carboxylate (0.571 g, 5 mmol), 1,2-dimethyl-piperazine (1.175 g, 5 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.311 g, 0.50 mmol) and cesium carbonate (2.281 g, 7.00 mmol) in toluene (50.0 ml) at 20° C. under nitrogen. The resulting suspension was stirred at 110° C. for 23 h. The crude product was purified by ion exchange chromatography, using a SCX2 column. The crude material was dissolved in methanol and then applied to the column. The desired product was eluted from the column using 2M NH3 in methanol and pure fractions were evaporated to dryness to afford the crude product as a brown oil. This material was further purified by silica column chromatography, eluting with a gradient of 1 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford ethyl 5-(3,4-dimethylpiperazin-1-yl)thiophene-2-carboxylate (0.640 g, 47.7%) as a light brown solid.

Fuente