Ethyl chloroformate → 2-Methyl-2-propanyl (2S,4S)-2-carbamoyl-4-fluoro-1-pyrrolidinecarboxylate

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Reaction Conditions

Reaction Steps

To a well stirred solution of (2S,4S)-1-(tert-butoxycarbonyl)-4-fluoropyrrolidine-2-carboxylic acid (50 g, 0.2145 mmol) in dry THF (1000 ml) was added TEA (32.49 g, 0.3217 mmol) at room temperature. The mixture was cooled to −10° C. and ethyl chloroformate (34.93 g, 0.3217 mmol) was added over period of 20 min. The mixture was stirred for 30 min at the same temperature under nitrogen atmosphere and aqueous ammonium hydroxide (500 ml) was added. The aqueous mixture was stirred at room temperature for 18 h and THF in the mixture was evaporated under reduced pressure. The aqueous mixture was further diluted with water (100 ml) and extracted with chloroform (3×100 ml). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure. The residue was stirred in petroleum ether (250 ml) for 20 min to give a white filterable solid. The product was collected by filtration and dried to give 44.7 g of the product as a white solid. 1H NMR (CDCl3, 300 MHz) δ 1.48 (s, 9H), 2.20-2.80 (m, 2H), 3.51-3.85 (m, 2H), 4.38 (br s, 1H), 5.21 (d, J=52.2 Hz, 1H), 5.50 (br s, 1H), 6.16 (br s, 0.5H, rotomer), 6.59 (br s, 0.5H, rotomer)

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