반응 #10375

반응 방정식

2,3,4,5-tetrafluorobenzoic acid ethyl ester

(S)-pyrrolidin-3-ylcarbamic acid tert-butyl ester

triethylamine

→

title compound

수율 74.5%

4-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2,3,5-trifluorobenzoic acid ethyl ester

수율 74.5%

용매

acetonitrile

반응 조건

후처리

1. 1
   농축The yellow solution is concentrated in vacuo
2. 2
   workup.ADDITIONpoured into a saturated NaHCO3 solution
3. 3
   추출The mixture is then extracted with chloroform
4. 4
   세척the combined organic extracts are washed with brine
5. 5
   건조dried with Na2SO4
6. 6
   여과filtered
7. 7
   농축concentrated in vacuo
8. 8
   기타The resulting residue is then purified by flash column chromatography (1:7 ethyl acetate/hexanes)

실험 절차

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).

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