Reacción #1253194

Ecuación de reacción

1-t-Butoxycarbonyl-3-oxopiperazine

potassium t-butoxide

1-(4-methylphenylsulfonyloxy)-2-fluoroethane

→

1-t-butoxycarbonyl-4-(2-fluoroethyl)-3-oxopiperazine

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITcontinued at the same temperature for 24 hours
3. 3
   OtroThe solvent is removed
4. 4
   Otrothe residue partitioned between ethyl acetate and water
5. 5
   LavadoThe organic phase is washed with water
6. 6
   Concentraciónconcentrated
7. 7
   workup.DISSOLUTIONThe residue is dissolved in isopropanol
8. 8
   workup.ADDITIONdiluted with iso-hexane forming a precipitate which
9. 9
   Otrois removed by filtration
10. 10
    OtroThe mixture is chromatographed (silica
11. 11
    Lavadoeluting with
12. 12
    Temperaturaa gradient increasing in polarity from 0 to 50% isopropanol in iso-hexane)

Procedimiento

1-t-Butoxycarbonyl-3-oxopiperazine (21.6 g) is dissolved in dry DMF (500 ml) and potassium t-butoxide (24.2 g) is added. The mixture is stirred at 20-25° for 30 minutes, then 1-(4-methylphenylsulfonyloxy)-2-fluoroethane (J. Med. Chem., 23(9), 985-90 (1980), 25.9 g) is added and stirring continued at the same temperature for 24 hours. The solvent is removed and the residue partitioned between ethyl acetate and water. The organic phase is washed with water and concentrated. The residue is dissolved in isopropanol and diluted with iso-hexane forming a precipitate which is removed by filtration. The mixture is chromatographed (silica; eluting with a gradient increasing in polarity from 0 to 50% isopropanol in iso-hexane) to give 1-t-butoxycarbonyl-4-(2-fluoroethyl)-3-oxopiperazine.

Fuente