Sodium hydride → HCID 66934466, compound

Participants

Reaction Conditions

Reaction Steps

NaH (60% in oil, prewashed with hexane; 2.76 g, 69.0 mmol) was suspended in anhydrous THF (100 mL) under nitrogen and the reaction mixture was cooled to 0° C. with stirring. A solution of (S)-3-hydroxymethyl-morpholine-4-carboxylic acid tert-butyl ester (5.00 g, 23.0 mmol) in THF (100 mL) was added dropwise. The reaction mixture was stirred for 30 minutes at 0° C. 4-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester (Intermediate 6; 10.0 g, 29.0 mmol) was added and the reaction mixture was stirred overnight at room temperature before standing for 24 h. The reaction mixture was cooled to 5-10° C. A 10% aqueous solution of NaHCO3 (22 mL) was added and the solvents were removed in vacuo. The residue was partitioned between EtOAc (700 mL) and 10% aqueous solution of NaHCO3 (200 mL)/water (400 mL). The EtOAc layer was dried (MgSO4) and the solvent removed in vacuo. The residue was purified by column chromatography (normal phase silica, 100 g Isolute-Si column, gradient of EtOAc in hexane). The residue was dissolved in DCM and evaporated in vacuo and repeated before drying in vacuo to give (3S)-3-[4-(4-fluorophenyl)-piperazine-1-carbonyloxymethyl]-morpholine-4-carboxylic acid tert-butyl ester (8.19 g, 84%) as an orange gum.

Provenance & Evidence