Diisopropylamine → tert-Butyl 4-formylpiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 15.9 mL of LDA (2 M solution in THF) in 25 mL of THF at −78° C. was added 36.6 mL of diisopropylamine followed by 15.9 ml of (trimethylsilyl)diazomethane dropwise. After stirring at −78° C. for 30 min, 5.25 g of tert-butyl-4oxo-1-piperidinecarboxylate in 10 mL of THF was added slowly over 10 min. The reaction was stirred at −78° C. for 1 hr. After refluxing for 4 hr, the reaction was quenched with cold water and extracted with 3×70 mL of EtOAc. The combined organic phases were dried over MgSO4 and concentrated. The residue was dissolved in 150 mL of EtOAc, then 10 g of silica gel was added. After stirring at rt for 16 hr, silica gel was filtered off. Concentration of filtrate followed by flash chromatography eluting with 25% EtOAc in hexane followed by 100% EtOAc afforded 3.66 g of the title compound as an oil.

Provenance & Evidence