Methyl iodide → 1-tert-Butyl 4-ethyl 4-methylpiperidine-1,4-dicarboxylate

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Reaction Conditions

Reaction Steps

n-Butyllithium (15% solution in n-hexane; 82 mL, 0.19 mol) is added to a stirred solution of diisopropyl amine (28.75 mL, 0.20 mol) in tetrahydrofuran (400 mL) at −70° C. under an atmosphere of nitrogen and stirred for 30 minutes. A solution of piperidine-1,4-dicarboxylic acid-1-tert-butyl ester 4-ethyl ester (30 g, 0.12 mol) in tetrahydrofuran (80 mL) is introduced at −70° C. Hexamethyl phosphoramide (45 mL) is added and reaction mixture is allowed to stir till the temperature reaches at −45° C. Reaction mixture again cooled to −70° C., methyl iodide (39.3 mL, 0.60 mol) is added and stirred for 1 hour. Saturated aqueous solution of ammonium chloride (100 mL) is added slowly into the reaction mixture at 0° C. and stirred for 10 minutes. It is extracted with ethyl acetate (3×200 mL). Combined organic layer is washed with brine solution (1×100 mL) and dried over sodium sulfate. Removal of solvent under reduced pressure gives a viscous liquid which is purified by column chromatography (silica gel 230-400, n-hexane:ethyl acetate, 9:1) to furnish 4-methyl piperidine-1,4-dicarboxylic acid-1-tert-butylester-4-ethyl ester.

Provenance & Evidence