Triethylamine → (trans)-3-Methyl-4-(2-oxo-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To an ice-cold solution of 4-amino-3-methyl-piperidine-1-carboxylic acid tert-butyl ester (2.5 g 12 mmol) and triethylamine (31 ml, 23 mmol) in CH2Cl2 (100 ml) was added 4-chlorobutyric acid chloride (11 ml, 14 mmol) and the reaction allowed to come to room temperature. The reaction was then washed with water, was dried (Na2SO4) and concentrated. The crude amide (1.9 g, 6 mmol) was redissolved in DMF (50 ml), cooled to 0° C. and sodium hydride (0.3 g, 12 mmol) was added portionwise. The mixture was allowed to reach room temperature, the reaction concentrated and the residue redissolved in CH2Cl2 and washed with saturated sodium hydrogen carbonate, dried (Na2SO4) and concentrated. Flash column chromatography (EtOAc:n-heptane 9:1-95:5) separated the title compounds affording (cis)-3-Methyl-4-(2-oxo-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (0.3 g, 18%) and (trans)-3-methyl-4-(2-oxo-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (0.63 g, 39%) as yellow oils. MS: 283.4 (MH+).

Provenance & Evidence