Acetic Acid → 4-((R)-2-Hydroxymethyl-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

A solution of 5.98 g (30.0 mmol) of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester and 3.55 ml=3.64 g (36.0 mmol) of (R)-(−)-pyrrolidin-2-yl-methanol in 60.0 ml of EtOH was treated with 60.0 ml of 1,2-dichloroethane, followed by 4.50 ml (36 mmol) of borane-pyridine complex (8 molar). Then, 4.46 ml=4.68 g (78.0 mmol) of acetic acid was added to this solution. After stirring at RT for 16 hours, the reaction mixture was poured into crashed ice; then, the pH was adjusted to 9-10 with sodium carbonate solution and the mixture was extracted twice with EtOAc; the combined organic phases were washed with water, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 8:2) to give 7.69 g (90%) of the title compound as light yellow oil. MS: 285.1 (MH+).

Provenance & Evidence