Triethylamine → 4-Oxo-piperidine-1-carboxylic acid diethylamide

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Reaction Steps

To a solution of piperidin-4-one in DMF was added triethylamine (1.5 eq.) and N,N-diethylacetamide chloride (1.5 eq.). The resulting solution was stirred at room temperature for 5 hours or until completion observed by TLC. The solvent was evaporated and the residue was partitioned in H2O and EtOAc. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by a CombiFlash chromatography system using silica gel cartridge and CH2Cl2/MeOH gradient eluent to afford 4-oxo-piperidine-1-carboxylic acid diethylamide, which was subsequently reacted with 3-hydroxybenzaldehyde (2.5 eq.) in acetic acid (99.7%) and purged with HCl gas (0.5-1 h). After stirring at room temperature for 3 hours, the solvent was evaporated and the crude was purified by a Combiflash chromatography system with hexanes/EtOAc as eluent, followed by crystallization from MeOH, to afford Compound 12 as a yellow crystalline solid.

Provenance & Evidence