Triethylamine → (S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl-2,3,5-trifluorobenzoic acid ethyl ester

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Reaction Steps

A solution of 2,3,4,5-tetrafluorobenzoic acid ethyl ester (Example 1a, 4.03 g, 18.1 mmol), (S)-pyrrolidin-3-ylcarbamic acid tert-butyl ester (4.02 g, 21.6 mmol) (Sanchez J. P., Domagala J. M., Heifetz C. L., Priebe S. R., Sesnie J. A., Trehan A. K., J. Med. Chem., 1992; 35(10):1764–1773), and triethylamine (18.0 mL, 129 mmol) in acetonitrile (50 mL) is heated at 50° C. under a nitrogen atmosphere for 4.5 hours. The yellow solution is concentrated in vacuo and poured into a saturated NaHCO3 solution. The mixture is then extracted with chloroform, and the combined organic extracts are washed with brine, dried with Na2SO4, filtered, and concentrated in vacuo. The resulting residue is then purified by flash column chromatography (1:7 ethyl acetate/hexanes) to afford the title compound (5.24 g). 1H NMR (CDCl3): δ 7.35 (ddd, 1H), 4.70–4.65 (bs, 1H), 4.42–4.20 (m, 3H), 3.90–3.62 (m, 3H), 3.58–3.42 (m, 1H), 2.28–2.03 (m, 1H), 1.99–1.80 (m, 1H), 1.46 (s, 9H), 1.37 (t, 3H).

Provenance & Evidence