Dimethylamine, hydrochloride → (2S,4R)-tert-butyl 2-(dimethylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

Participants

Reaction Steps

1-[3-(Dimethylamino)propyl]-3-ethylearbodiimide hydrochloride (2.48 g) was added to a stirred suspension of N-tert-butoxycarbonyl-L-hydroxyproline (2.0 g), 4-(dimethylamino)pyridine (5.28 g) and dimethylamine hydrochloride (1.4 g) in methylene chloride (100 ml) and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with citric acid (1.0 M), saturated sodium bicarbonate and saturated brine before drying over magnesium sulfate. The product was then purified by column chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10). The fractions containing the expected product were combined and evaporated under vacuum to give (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2-(N,N-dimethylcarbamoyl)pyrrolidine as a colourless gum (1.01 g); 1H NMR Spectrum: (DMSO d6) 1.29-1.40 (m, 9H), 1.74-1.83 (m, 1H), 2.04-2.15 (m, 1H), 2.80-2.87 (m, 3H), 3.03 (s, 3H), 3.26 (m, 1H), 3.40 (m, 1H), 4.28 (m, 1H), 4.64 (m, 1H), 4.95 (d, 1H).

Provenance & Evidence