3-(t-Butyl-amino)-N-methoxy-N-methyl-propanamide → 1-tert-Butyl-4-piperidone

Participants

Reaction Conditions

Reaction Steps

3-(t-Butyl-amino)-N-methoxy-N-methyl-propanamide (5 g, 26.6 mmol, 1.0 equiv) was dissolved in dry THF (50 mL) under Ar. The solution was cooled to −78° C. and a 1 M solution of vinylmagnesium bromide (66.5 mL, 66.5 mmol, 2.5 equiv) was added dropwise over a 20 min period. The reaction was then stirred at −78° C. for 30 min and at 0° C. for 30 min at which time the reaction solution was transferred via a double-ended cannula into ice-cold saturated sodium bicarbonate solution under Ar. The mixture was stirred for 10 min and the crude product was extracted 2×150 mL EtOAc. The organic extracts were combined and concentrated in vacuo to a red oil. Purification was done by flash chromatography on silica using 100% CH2Cl2 through 4, 8, and 16% MeOH in CH2Cl2. The product was isolated as an orange oil (1.3 g, 32%); MS, m/z 156=M+1.

Provenance & Evidence