Sodium Carbonate → Ethyl 4-(4-(benzyloxycarbonylamino)piperidin-1-yl)benzoate

Participants

Reaction Conditions

Reaction Steps

4-Fluorobenzoic acid ethyl ester (25.0 g, 149 mmol) was dissolved in dimethyl sulfoxide (hereinafter referred to as DMSO) (100 mL), and potassium carbonate (31.0 g, 224 mmol) and 4-aminopiperidine (18.8 mL, 177 mmol) were added thereto, followed by stirring at 130° C. for 20 hours. After the reaction mixture was cooled to room temperature, water was added to the mixture and the precipitate was collected by filtration, thereby giving ethyl 4-(4-aminopiperidin-1-yl)benzoate (36.0 g, 98%) as a yellow solid. This amino compound (15.7 g, 63.2 mmol) was dissolved in THF (200 mL), and a 2N sodium carbonate aqueous solution (63 mL) was added thereto. Subsequently, benzyloxycarbonyl chloride (11.7 mL, 82.2 mmol) was added to the mixture, followed by stirring at room temperature for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated sodium chloride aqueous solution, and then dried over anhydrous sodium sulfate. After the desiccant was filtered off, the solvent was evaporated under reduced pressure to precipitate a solid, which was collected by filtration and dried under reduced pressure, thereby giving the title compound (18.0 g, 74%) as a white solid.

Provenance & Evidence