Sodium hydride → 3-(4-Phenyl-piperazine-1-carbonyloxymethyl)-morpholine-4-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

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%).

Provenance & Evidence