3-Methoxybenzoic Acid → HCID 53255539, compound

Participants

Reaction Steps

To a DMF (780 mL) suspension of tert-butyl 4-aminopiperidine-1-carboxylate (78.0 g) and 3-methoxybenzoic acid (65.2 g), Et3N (130 mL), HOBt.H2O (71.7 g) and EDC.HCl (82.8 g) were added and the mixture was stirred at room temperature for 12 hours. H2O (1.56 L) was added and the mixture was stirred in a water bath for 1.5 hours. The precipitation was filtrated to obtain tert-butyl 4-[(3-methoxybenzoyl)amino]piperidine-1-carboxylate (126 g, a colorless solid substance). To an EtOAc (900 mL) suspension of the compound obtained in the above process, 4 M HCl/EtOAc solution (900 mL) was added and the mixture was stirred at room temperature for 4 hours. The reaction solution was concentrated under reduced pressure, and thereafter, CHCl3 (2.00 L) and 2 M aqueous NaOH solution (1.00 L) were added to the residue and the mixture was stirred for 15 minutes. A water layer was separated from an organic layer and thereafter extracted twice with CHCl3 (800 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to obtain 3-methoxy-N-piperidin-4-ylbenzamide (87.8 g, a light yellow solid).

Provenance & Evidence