Trifluoroacetic acid → Benzyl ((3R,4R)-4-fluoropyrrolidin-3-yl)carbamate

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Reaction Steps

To a solution of tert-butyl (3R,4R)-3-{[(benzyloxy)carbonyl]amino}-4-fluoropyrrolidine-1-carboxylate (380 mg, 1.2 mmol) in DCM (20 mL) was added TFA (0.34 mL, 3.4 mmol, 3 mol eq). The resulting reaction was stirred at ambient temperature for 2 hr. More TFA (0.34 mL, 3.4 mmol, 3 mol eq) was added and stirring at ambient temperature continued for another 2 hr. The volatiles were removed to give a colorless residue. DCM (30 mL) and aqueous K2CO3 (1 M, 5 mL) were added. The organic layer was separated, extracted with more DCM (30 mL), dried over Na2SO4 and evaporated to give the title compound as a colorless gum (246 mg, 92% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 7.29-7.43 (m, 5 H) 4.80-5.21 (m, 4 H) 4.07-4.28 (m, 1 H) 3.46 (br. s., 1 H) 2.96-3.30 (m, 2 H) 2.74 (br. s., 1 H). 19F NMR (376 MHz, chloroform-d) δ ppm −72.38 (s, 1F). m/z (APCI+) for C12H15FN2O2 239.2 (M+H)+. Chiral purity was determined as below (using the racemic sample to compare):

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