Triethylamine → tert-Butyl (2S,4S)-2-cyano-4-fluoropyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of tert-butyl (2S,4S)-2-carbamoyl-4-fluoropyrrolidine-1-carboxylate (50 g, 0.2155 mmol) in dry dichloromethane (500 ml) was added triethylamine (87.06 g, 0.862 mmol) and the mixture was cooled to 0° C. Trifluoroacetic anhydride (58.83 g, 0.2801 mmol) was added over period of 10 min and the mixture was stirred for 30 min at same temperature under nitrogen atmosphere. The mixture was diluted with water (300 ml) and the layers were separated. The aqueous layer was extracted with dichloromethane (100 ml). The combined organic phase was washed with 1N HCl (200 ml), 5% aqueous NaHCO3 (100 ml) and water (2×300 ml). The solution was dried over anhydrous Na2SO4 and then evaporated under reduced pressure to give 45 g of the product as a pale yellow solid; 1H NMR (CDCl3, 300 MHz) δ 1.49-1.53 (d, 9H, rotomer), 2.25-2.47 (m, 1H), 2.64 (t, J=14.7 Hz, 1H), 3.52 (dd, J=9.6, 3.6 Hz, 0.5H, rotomer), 3.64 (dd, J=9.3, 3.3 Hz, 0.5H, rotomer), 3.73-3.94 (m, 1H), 4.64 (d, J=8.7 Hz, 0.6H, rotomer), 4.76 (d, J=8.7 Hz, 0.4H, rotomer), 5.31 (br d, J=51.3 Hz, 1H).

Provenance & Evidence