Reaktion #2349679

Reaktionsgleichung

1-(4-chlorophenyl)-piperazine dihydrochloride

(4-Methyl-morpholin-2-yl)-methanol

DIPEA

HCl

Et2O

p-nitrophenyl chloroformate

→

(4-methylmorpholin-2-yl)methyl 4-(4-chlorophenyl)piperazine-1-carboxylate dihydrochloride salt

Ausbeute 119.5%

Lösungsmittel

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm to room temperature
2. 2
   Einengenconcentrated in vacuo
3. 3
   workup.DISSOLUTIONOne portion was dissolved in DMF (20 mL)
4. 4
   Sonstigethe resulting reaction mixture
5. 5
   workup.STIRRINGwas stirred at room temperature for 24 h
6. 6
   SonstigeThe solvent was removed in vacuo
7. 7
   workup.DISSOLUTIONthe residue was dissolved in DCM (30 mL)
8. 8
   WaschenThe organic layer was washed with 1.0M Na2CO3 solution (3×30 mL)
9. 9
   Trocknendried (MgSO4)
10. 10
    Sonstigethe solvents were removed in vacuo
11. 11
    SonstigeThe residue was purified by column chromatography (normal phase, 20 g, Strata SI-1, silica gigatube, 20 mL/min, gradient 0% to 5% MeOH in DCM, residue dry loaded)
12. 12
    SonstigeThe solvents were removed in vacuo
13. 13
    workup.DISSOLUTIONthe residue was dissolved in DCM (50 mL)
14. 14
    Filtrationfiltered
15. 15
    SonstigeThe solvents were removed in vacuo
16. 16
    Sonstigethe resulting solid was dried in a vacuum oven overnight

Vorschrift

(4-Methyl-morpholin-2-yl)-methanol (1.05 g, 8.0 mmol) and DIPEA (2.79 ml, 16.0 mmol were dissolved in DCM (80 mL) and the reaction mixture was cooled to 0° C. and p-nitrophenyl chloroformate (3.23 g, 16.0 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was divided into 4 batches and concentrated in vacuo. One portion was dissolved in DMF (20 mL) and 1-(4-chlorophenyl)-piperazine dihydrochloride (539 mg, 2 mmol) was added, and the resulting reaction mixture was stirred at room temperature for 24 h. The solvent was removed in vacuo and the residue was dissolved in DCM (30 mL). The organic layer was washed with 1.0M Na2CO3 solution (3×30 mL), dried (MgSO4) and the solvents were removed in vacuo. The residue was purified by column chromatography (normal phase, 20 g, Strata SI-1, silica gigatube, 20 mL/min, gradient 0% to 5% MeOH in DCM, residue dry loaded). The solvents were removed in vacuo and the residue was dissolved in DCM (50 mL), filtered and 2M HCl in Et2O (2 mL, 4 mmol) added. The solvents were removed in vacuo and the resulting solid was dried in a vacuum oven overnight to give the (4-methylmorpholin-2-yl)methyl 4-(4-chlorophenyl)piperazine-1-carboxylate dihydrochloride salt (0.510 g, 60%) as a white solid.

Quelle