Reacción #2846

Ecuación de reacción

(2-oxo-pyrrolidin-3-(S)-yl)-carbamic acid tert-butyl ester

4-bromomethyl-thiophene-2-carbonitrile

sodium hydride

→

title compound

Rendimiento 86.3%

[1-(5-Cyanothiophene-3-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-carbamic acid tert-butyl ester

Rendimiento 86.3%

Disolventes

THF DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONAfter addition
2. 2
   Temperaturato warm to ambient temperatures
3. 3
   Otrothe solution is quenched by the addition of sat. NH4Cl
4. 4
   workup.ADDITIONThe solution is diluted with H2O and EtOAc
5. 5
   OtroThe layers are separated
6. 6
   LavadoThe organic layer is washed with H2O and sat. NaCl
7. 7
   SecadoThe organic layer is dried over MgSO4
8. 8
   Filtraciónfiltered
9. 9
   Concentraciónconcentrated
10. 10
    OtroThe crude product is purified by column chromatography
11. 11
    Lavadoeluting with gradient of 20% EtOAc/CH2 Cl2 to 30% EtOAc/CH2Cl2

Procedimiento

To a solution of (2-oxo-pyrrolidin-3-(S)-yl)-carbamic acid tert-butyl ester (3.2 g, 16 mmol), prepared as described in EXAMPLE 1, Part A in 80 mL of THF:DMF (10:1) at 0° C. is added 4-bromomethyl-thiophene-2-carbonitrile (3.23 g, 16 mmol) and sodium hydride (60% dispersion in oil, 0.67 g, 16.8 mmol). After addition, the solution was allowed to warm to ambient temperatures. After 2 h, the solution is quenched by the addition of sat. NH4Cl. The solution is diluted with H2O and EtOAc. The layers are separated. The organic layer is washed with H2O and sat. NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with gradient of 20% EtOAc/CH2 Cl2 to 30% EtOAc/CH2Cl2 to afford the title compound (4.0 g, 13.8 mmol) as a white solid.

Fuente