反应详情

温度

0 °C

(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.

1. temperatureto warm to room temperature
2. concentrationconcentrated in vacuo
3. dissolutionOne portion was dissolved in DMF (20 mL)
4. customthe resulting reaction mixture
5. stirringwas stirred at room temperature for 24 h
6. customThe solvent was removed in vacuo
7. dissolutionthe residue was dissolved in DCM (30 mL)
8. washThe organic layer was washed with 1.0M Na2CO3 solution (3×30 mL)
9. dry with materialdried (MgSO4)
10. customthe solvents were removed in vacuo
11. customThe 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. customThe solvents were removed in vacuo
13. dissolutionthe residue was dissolved in DCM (50 mL)
14. filtrationfiltered
15. customThe solvents were removed in vacuo
16. customthe resulting solid was dried in a vacuum oven overnight