Diisopropylethylamine → rac-(3S,4R)-{4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-carbamic acid tert-butyl ester

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Reaction Steps

To a solution of 1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid (4.48 g, 0.02 mol) in DMF (40 ml) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (9.54 g, 0.03 mol). After stirring for 10 min at ambient temperature N,N-diisopropyl ethyl amine (19.82 ml, 0.116 mol) and a solution of rac-(3S,4R)-[4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (6.39 g, 67% purity, 0.013 mol) in DMF (45 ml) were added and the reaction mixture was stirred for 19 h at this temperature. It was diluted with ethyl acetate (80 mL) and the organic layer was washed with water (80 mL), aqueous sodium carbonate (1M, 40 mL) and brine (40 mL). The aqueous layers were extracted with ethyl acetate (160 mL). the combined organic layers were dried over sodium sulfate and concentrated. Purification by flash chromatography (SiO2, EtOAc/methanol 100:0 to 80:20) afforded 5.84 g (87%) of the title compound as a light brown foam. ES-MS m/e: 524.1 (M+H+).

Provenance & Evidence