Sodium hydride → HCID 66934484, compound

Participants

Reaction Conditions

Reaction Steps

NaH (60% in oil, prewashed with hexane; 1.38 g, 34.5 mmol) was suspended in anhydrous THF (50 mL) under nitrogen, the reaction mixture cooled to −5° C. with stirring and a solution of (R)-3-hydroxymethyl-morpholine-4-carboxylic acid tert-butyl ester (2.50 g, 11.5 mmol) in THF (50 mL) was added dropwise. The reaction mixture was stirred for 30 min at 0 to 3° C. 4-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester (Intermediate 6; 5.01 g, 14.5 mmol) was added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was cooled with an ice bath and a 10% aq NaHCO3 solution (11 mL) was added. The solvents were removed in vacuo and the residue was partitioned between EtOAc (350 mL) and 10% aq NaHCO3 solution (100 mL)/water (200 mL). The EtOAc layer was dried (MgSO4) and the solvent removed in vacuo. The residue was purified by column chromatography (normal phase silica, 70 g Isolute-Si column, gradient of EtOAc in hexane). The residue was dissolved in DCM and evaporated in vacuo and repeated once before drying in vacuo to give (3R)-3-[4-(4-fluorophenyl)-piperazine-1-carbonyloxymethyl]-morpholine-4-carboxylic acid tert-butyl ester (2.80 g) as a pale yellow gum.

Provenance & Evidence