Reaktion #2349663

Reaktionsgleichung

4-nitrophenyl 4-phenylpiperazine-1-carboxylate

Intermediate 2

4-nitrophenyl 4-phenylpiperazine-1-carboxylate

1,4-dimethyl-(S)-2-hydroxymethyl piperazine

Intermediate 3

1,4-dimethyl-(S)-2-hydroxymethyl piperazine

sodium hydride

→

[(2S)-1,4-dimethylpiperazin-2-yl]methyl 4-phenylpiperazine-1-carboxylate

Ausbeute 36.5%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm to room temperature
2. 2
   workup.STIRRINGstirred for 7 hours
3. 3
   TemperaturThe reaction mixture was then cooled to 0° C.
4. 4
   Sonstigequenched with the drop-wise addition of sat aq NaHCO3 solution
5. 5
   SonstigeThe THF was removed in vacuo
6. 6
   Extraktionthe aqueous phase extracted with EtOAc (×3)
7. 7
   Waschenwashed with sat aq NaHCO3 solution (×6)
8. 8
   Trocknendried (MgSO4)
9. 9
   Einengenconcentrated in vacuo
10. 10
    Filtrationformic acid solution [1:1] (20 mL), filtered
11. 11
    Sonstigethe filtrate was purified by reverse phase column chromatography (gradient
12. 12
    Wascheneluting with methanol in water, with 1% formic acid in each solvent, 0-15%)
13. 13
    workup.DISSOLUTIONThe resulting residue was dissolved in DCM (50 mL)
14. 14
    workup.STIRRINGstirred with solid K2CO3 for 20 minutes
15. 15
    Filtrationfiltered
16. 16
    Einengenconcentrated in vacuo

Vorschrift

To a solution of 1,4-dimethyl-(S)-2-hydroxymethyl piperazine (Intermediate 3; 1.49 g, 10.3 mmol) in THF (20 mL) at 0° C. was added sodium hydride (1.24 g, 60% dispersion in mineral oil, 31.0 mmol). The reaction mixture was stirred for several minutes at 0° C. and then 4-nitrophenyl 4-phenylpiperazine-1-carboxylate (Intermediate 2; 3.72 g, 11.4 mmol) in THF (20 mL). The reaction mixture was allowed to warm to room temperature and stirred for 7 hours. The reaction mixture was then cooled to 0° C. and quenched with the drop-wise addition of sat aq NaHCO3 solution. The THF was removed in vacuo, the aqueous phase extracted with EtOAc (×3), combined organic phases washed with sat aq NaHCO3 solution (×6), dried (MgSO4) and concentrated in vacuo. The residue was suspended in water: formic acid solution [1:1] (20 mL), filtered and the filtrate was purified by reverse phase column chromatography (gradient eluting with methanol in water, with 1% formic acid in each solvent, 0-15%). The resulting residue was dissolved in DCM (50 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give [(2S)-1,4-dimethylpiperazin-2-yl]methyl 4-phenylpiperazine-1-carboxylate (1.25 g, 36%) as a pale yellow solid.

Quelle