反应详情

温度

0 °C

NaH (60% in oil, prewashed with hexane; 0.91 g, 22.9 mmol) was suspended in anhydrous THF (25 mL) under nitrogen and cooled to 0° C. with stirring. A solution of (4-methyl-morpholin-3-yl)-methanol (1.00 g, 2.62 mmol) in THF (25 mL) was added dropwise. 4-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester (Intermediate 6; 3.16 g, 9.15 mmol) was added and the reaction mixture was stirred overnight at room temperature. A saturated aqueous solution of NaHCO3 (10 mL) was added and the solvents were removed in vacuo. The residue was partitioned between water and EtOAc and the aqueous phase was extracted with EtOAc. The combined organic extracts were washed with sat aq NaHCO3 (3×100 mL), dried (MgSO4) and the solvents were removed in vacuo. The residue was purified by flash normal column chromatography (Apollo silica, 40-63 μm, 60 A) eluting with 1% MeOH in DCM to give (4-methylmorpholin-3-yl)methyl 4-(4-fluorophenyl)piperazine-1-carboxylate (2.15 g, 83%) as a white solid.

1. stirringthe reaction mixture was stirred overnight at room temperature
2. customthe solvents were removed in vacuo
3. customThe residue was partitioned between water and EtOAc
4. extractionthe aqueous phase was extracted with EtOAc
5. washThe combined organic extracts were washed with sat aq NaHCO3 (3×100 mL)
6. dry with materialdried (MgSO4)
7. customthe solvents were removed in vacuo
8. customThe residue was purified by flash normal column chromatography (Apollo silica, 40-63 μm, 60 A)
9. washeluting with 1% MeOH in DCM