Tert-butyl 3-oxopiperidine-1-carboxylate → HCID 66784471, compound

Participants

Reaction Conditions

Reaction Steps

Into a 50 mL round bottomed flask was added 5-tert-butyl-1-(3-methoxypropyl)-1H-imidazole (133A) (376 mg, 1.9 mmol) and THF (9.6 mL). The solution was cooled to −78° C. and n-BuLi (843 μL, 2.5 M/hexanes, 2.1 mmol) was added slowly via syringe. The mixture was stirred for 20 minutes and slowly warmed to −30° C. The solution was cooled to −78° C. and N-Boc-3-piperidone (418 mg, 2.1 mmol) in THF (5 mL) was added slowly via syringe; the mixture was allowed to warm to room temperature overnight. Solvent was removed under vacuum and the residue was partitioned between water (25 mL) and ethyl acetate (25 mL). The organic layer was separated and discarded. The aqueous layer extracted with ethyl acetate (2×25 mL). The organic portions were combined and washed with brine (50 mL) and dried over sodium sulfate and filtered. The solvent was removed in vacuo and the residue was purified by preparatory LC/MS (10-45% CH3CN in H2O) to give tert-butyl 3-(5-tert-butyl-1-(3-methoxypropyl)-1H-imidazol-2-yl)-3-hydroxypiperidine-1-carboxylate (133B) as a yellow oil (160 mg, 21% yield). ESI-MS:m/z 396.5 (M+H)+.

Provenance & Evidence