Ethanol → (S)-tert-butyl 3-(2-ethoxy-2-oxoethyl)pyrrolidine-1-carboxylate

Participants

Reaction Steps

In an oven-dried 2 L round bottom flask under nitrogen, ((3S)-1-{[(1,1-dimethylethyl)oxy]carbonyl}-3-pyrrolidinyl)acetic acid (60 g, 262 mmol) dissolved in diethyl ether (600 mL) was treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (55.2 g, 288 mmol), 4-(dimethylamino)pyridine (3.20 g, 26.2 mmol), and ethanol (33.6 ml, 576 mmol) at room temperature and the mixture was stirred for 40 h. The reaction mixture began as a white suspension, but then became a pale yellow solution with gummy yellow material at the bottom of the flask after 1 h, which was difficult to stir. Another stir bar was added in order to get the mixture stirring; however, a vortex was not obtained so the reaction was stirred longer than overnight to ensure the reaction went to completion. The reaction mixture was diluted with ether (400 mL) and washed with 1M aqueous sodium hydrogen sulfate solution (800 mL) and saturated aqueous sodium bicarbonate solution (800 mL). The organic phase was isolated, dried over magnesium sulfate, and concentrated to dryness to give the title compound as a clear pale yellow liquid (64.1 g, 249 mmol, 95%). MS(ES)+ m/e 258.2 [M+H]+, 280.2 [M+Na]+.

Provenance & Evidence