Triethylamine → (R)-Tert-butyl 3-(methoxy(methyl)carbamoyl)pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

In a 500 mL round-bottomed flask under a positive pressure of nitrogen, was added a methylene chloride (125 mL) solution of (R)—N-Boc-pyrroldine-3-carboxylic acid (7.00 g, 0.0325 mol). This solution was cooled to 0° C. using an ice/water bath and treated sequentially with, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (7.48 g, 0.0390 mol) and 1-hydroxybenzotriazole (5.29 g, 0.0391 mol) in single portions. Following the addition of the coupling agents, the reaction mixture became cloudy, but upon further stirring a clear solution was obtained. The reaction mixture was stirred at 0° C. for 20 min then charged with N,O-dimethylhydroxylamine hydrochloride (4.78 g, 0.0490 mol) and triethylamine (13.5 mL, 0.0968 mol). The cooling bath was removed and the reaction mixture was allowed to warm to room temperature with stirring over a period of 1 h. The resulting solution was diluted with dichloromethane (600 mL) and 1 N HCl (1000 mL), mixed thoroughly and separated. The organic layer was washed with saturated aqueous sodium bicarbonate (300 mL) and saturated aqueous sodium chloride (300 mL), then dried over Na2SO4, filtered and concentrated to give tert-butyl (3R)-3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylate as a colorless oil (7.00 g; 83%). 1H NMR (400 MHz, CDCl3) δ 3.73 (s, 3H), 3.60-3.37 (m, 4H), 3.21 (s, 3H), 2.35-2.09 (m, 3H) 1.47 (s, 9H); ESI MS found for C12H22N2O4 m/z [159.1 (M+1-Boc)]

Provenance & Evidence