反应详情

温度

0 °C

NaH (60% in oil, prewashed with hexane; 1.23 g, 30.1 mmol) was suspended in anhydrous THF (50 mL) under nitrogen and cooled to 0° C. with stirring. A solution of 3-hydroxymethyl-morpholine-4-carboxylic acid tert-butyl ester (Intermediate 7; 2.23 g, 10.3 mmol) in THF (50 mL) was added dropwise. The reaction mixture was stirred for 20 min at 0° C. 4-Nitrophenyl 4-phenylpiperazine-1-carboxylate (Intermediate 2; 4.03 g, 12.3 mmol) was added and the reaction mixture was stirred for 48 h at room temperature. A sat aq NaHCO3 solution (10 mL) was added and the solvents were removed in vacuo. The residue was partitioned between water and EtOAc, the aqueous phase was extracted with EtOAc (2×100 mL). 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 3-(4-phenyl-piperazine-1-carbonyloxymethyl)-morpholine-4-carboxylic acid tert-butyl ester (3.35 g, 80%).

1. stirringThe reaction mixture was stirred for 20 min at 0° C
2. stirringthe reaction mixture was stirred for 48 h at room temperature
3. customthe solvents were removed in vacuo
4. customThe residue was partitioned between water and EtOAc
5. extractionthe aqueous phase was extracted with EtOAc (2×100 mL)
6. washThe combined organic extracts were washed with sat aq NaHCO3 (3×100 mL)
7. dry with materialdried (MgSO4)
8. customthe solvents were removed in vacuo
9. customThe residue was purified by flash normal column chromatography (Apollo silica, 40-63 μm, 60 A)
10. washeluting with 1% MeOH in DCM