Reacción #10375

Ecuación de reacción

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

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

triethylamine

→

title compound

Rendimiento 74.5%

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

Rendimiento 74.5%

Disolventes

acetonitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   ConcentraciónThe yellow solution is concentrated in vacuo
2. 2
   workup.ADDITIONpoured into a saturated NaHCO3 solution
3. 3
   ExtracciónThe mixture is then extracted with chloroform
4. 4
   Lavadothe combined organic extracts are washed with brine
5. 5
   Secadodried with Na2SO4
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated in vacuo
8. 8
   OtroThe resulting residue is then purified by flash column chromatography (1:7 ethyl acetate/hexanes)

Procedimiento

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).

Fuente