Reacción #75543

Ecuación de reacción

sodium sulfate

N-methylpiperazine

methyl 2-acetamidoacrylate

→

methyl 2-(acetylamino)-3-(4-methyl-piperazinyl)propanoate

Disolventes

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONare added
2. 2
   workup.STIRRINGwhile stirring the reaction mixture
3. 3
   Filtraciónthe mixture filtered through Celite
4. 4
   OtroAfter separation of the phase
5. 5
   Secadothe organic phase is dried over sodium sulfate
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated in a vacuum oven under reduced pressure (2 kPa) at a temperature of about 40° C. in order
8. 8
   Otroto obtain an orange-colored liquid
9. 9
   ExtracciónThe aqueous phase is extracted with 3 times 150 mL of dichloromethane
10. 10
    Otroall of the organic extracts are collected
11. 11
    Secadodried over sodium sulfate
12. 12
    Concentraciónconcentrated under reduced pressure (2 kPa) at a temperature of about 20° C. in order
13. 13
    Otroto obtain an yellow oil
14. 14
    Otropurified by chromatography under argon pressure (50 kPa)
15. 15
    Lavadoon a column of silica gel (particle size 40-63 μm; diameter 5 cm; height 25 cm), eluting with successive mixtures of 20% dichloromethane/methanol/aqueous ammonia (99/1/0, 97/3/0, 90/10/0.25, 80/20/0.25 by volume)
16. 16
    workup.ADDITIONThe fractions containing the expected product
17. 17
    Concentraciónconcentrated under reduced pressure (2 kPa) at a temperature of about 30° C

Procedimiento

To a solution of 8.57 g of methyl 2-acetamidoacrylate in 500 mL of dichloromethane stirred under inert atmosphere, about 6.65 mL of N-methylpiperazine are added, then 0.97 g of iron trichloride are added, and the mixture is stirred at a temperature of about 20° C. for 66 hours. Then, 300 mL of an aqueous solution of sodium sulfate are dropped to the reaction medium while stirring the reaction mixture and the mixture filtered through Celite. After separation of the phase by settling, the organic phase is dried over sodium sulfate, filtered and then concentrated in a vacuum oven under reduced pressure (2 kPa) at a temperature of about 40° C. in order to obtain an orange-colored liquid. The aqueous phase is extracted with 3 times 150 mL of dichloromethane and all of the organic extracts are collected, dried over sodium sulfate, then concentrated under reduced pressure (2 kPa) at a temperature of about 20° C. in order to obtain an yellow oil. Both of the organic extracts as described above are combined and purified by chromatography under argon pressure (50 kPa), on a column of silica gel (particle size 40-63 μm; diameter 5 cm; height 25 cm), eluting with successive mixtures of 20% dichloromethane/methanol/aqueous ammonia (99/1/0, 97/3/0, 90/10/0.25, 80/20/0.25 by volume). The fractions containing the expected product are combined and concentrated under reduced pressure (2 kPa) at a temperature of about 30° C. About 3.3 g of methyl 2-(acetylamino)-3-(4-methyl-piperazinyl)propanoate are obtained in the form of a yellow liquid. [Infrared spectrum CCl4 3437; 3318; 2941; 2798; 1749; 1685; 1499; 1458; 1374; 1286; 1204; 1168 and 1014 cm−1]

Fuente