Triethylamine → 4-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2,3,6-trifluorobenzoic acid ethyl ester

HRID 10280Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 10280
[CH2:1]([O:3][C:4](=[O:15])[C:5]1[C:10]([F:11])=[CH:9][C:8](F)=[C:7]([F:13])[C:6]=1[F:14])[CH3:2].C(N(CC)CC)C.[C:23]([O:27][C:28](=[O:35])[NH:29][C@H:30]1[CH2:34][CH2:33][NH:32][CH2:31]1)([CH3:26])([CH3:25])[CH3:24]>C(#N)C>[CH2:1]([O:3][C:4](=[O:15])[C:5]1[C:10]([F:11])=[CH:9][C:8]([N:32]2[CH2:33][CH2:34][C@H:30]([NH:29][C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:35])[CH2:31]2)=[C:7]([F:13])[C:6]=1[F:14])[CH3:2]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 210411752,3,4,6-Tetrafluorobenzoic acid ethyl ester

Produkt 1

HCID 586818974-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2,3,6-trifluorobenzoic acid ethyl esterAusbeute 69,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

A solution of 2,3,4,6-tetrafluorobenzoic acid ethyl ester (Example 1b, 5.1 g, 22.9 mmol), triethylamine (22 mL, 157 mmol), and (S)-pyrrolidin-3-ylcarbamic acid tert-butyl ester (5.2 g, 27.9 mmol) in acetonitrile (60 mL) is stirred at room temperature for 64 hours. The mixture is concentrated in vacuo and the residue dissolved in chloroform, washed with NaHCO3 and then brine, dried over Na2SO4, filtered, and concentrated under vacuum to afford a solid. The solid is purified by column chromatography (1:1:7 ethyl acetate/chloroform/hexanes) to afford the title compound (6.21 g). 1H NMR (CDCl3): δ 6.07 (ddd, 1H), 4.78–4.63 (bd, 1H), 4.49–4.22 (m, 3H), 3.80–3.68 (m, 1H), 3.66–3.28 (m, 3H), 2.33–2.13 (m, 1H), 2.04–1.83 (m, 1H), 1.45 (s, 9H), 1.36 (t, 3H).

Aufarbeitung

  1. concentrationThe mixture is concentrated in vacuo
  2. dissolutionthe residue dissolved in chloroform
  3. washwashed with NaHCO3
  4. dry with materialbrine, dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customto afford a solid
  8. customThe solid is purified by column chromatography (1:1:7 ethyl acetate/chloroform/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-acbacd71398448cdac9007290ea3a3a2
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07094780B1

Notizen zur Reaktion

Wird geladen…