4-Acetylpyridine → 4-(3,5-Dioxo-5-pyridin-4-ylpentyl)piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

CDI (0.63 g, 3.9 mmol) was added to a solution of 4-(2-carboxyethyl)piperidine-1-carboxylic acid tert-butyl ester (1.00 g, 3.9 mmol) in anhydrous THF (7.6 ml), then the mixture was stirred for 45 min. In a separate vessel, 4-acetylpyridine (0.49 g, 4.1 mmol) was added slowly to a stirred solution of LDA (2.04 ml of a 2.0M solution in heptane-THF-ethylbenzene, 4.1 mmol) in anhydrous THF (15.3 ml) at −78° C. After 45 min, the solution of the acylimidazole was added slowly via cannula to the lithiated 4-acetylpyridine while maintaining the temperature at −78° C. The reaction was allowed to warm to rt over 2 h, before being diluted with EtOAc (150 ml). The solution was washed with 10% aqueous citric acid (2×15 ml), saturated aqueous NaHCO3 (2×15 ml), and brine (20 ml), before being dried (MgSO4). Filtration, concentration, and purification by RP-HPLC afforded the title compound: m/z (ES+)=261.2 [M-Boc+H]+.

Provenance & Evidence