4-Vinylpyridine → 5-(2-(4-Pyridinyl)vinyl)-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine

HRID 2305117Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2305117
Br[C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:13][CH2:12][N:11]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:5]=[N:6][CH:7]=1.[CH:21]([C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)=[CH2:22].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)C.C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:26]1[CH:27]=[CH:28][C:23]([CH:21]=[CH:22][C:2]2[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]3[CH2:13][CH2:12][N:11]3[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:5]=[N:6][CH:7]=2)=[CH:24][CH:25]=1

Komponenten

7

Edukt 3

HCID 75024-VinylpyridineHCID 80271Tri-o-tolylphosphineHCID 10688713(S)-Tert-butyl 2-(((5-bromopyridin-3-YL)oxy)methyl)azetidine-1-carboxylate

Produkt 1

HCID 538525935-(2-(4-Pyridinyl)vinyl)-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridineAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 6342AcetonitrileLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a solution of 5-bromo-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from step 54b (1.03 g, 3.0 mmol) in acetonitrile (20 mL) and triethylamine (12.5 mL) was added 4-vinylpyridine (0.65 mL, 6 mmol), palladium acetate (125 mg, 0.56 mmol) and tri-o-tolylphosphine (625 mg). The mixture was heated at reflux for 16 hours. The solvent was removed, and the residue was washed with saturated sodium bicarbonate was added to free the amine, and the mixture was extracted with EtOAc, dried (MgSO4), and concentrated. The residue was chromatographed on a silica gel column, eluting with hexane:Et2O 1:2 to 0:1 to afford the title compound (760 mg, 69%). MS (CI/NH3) m/z 368 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.43 (s, 9H), 2.35 (m, 2H), 3.90 (m, 2H), 4.20 (m, 1H), 4.40 (m, 1H), 4.55 (m, 1H), 7.10 (m, 1H), 7.2 (m, 1H), 7.38 (m, 2H), 7.45 (br s, 1H), 8.29 (m, 1H), 8.37 (s, 1H), 8.61 (m, 2H).

Aufarbeitung

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 16 hours
  3. customThe solvent was removed
  4. washthe residue was washed with saturated sodium bicarbonate
  5. additionwas added
  6. extractionthe mixture was extracted with EtOAc
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was chromatographed on a silica gel column
  10. washeluting with hexane:Et2O 1:2 to 0:1

Quellen und Nachweise

ORD-Eintrag
ord-f29aa3d538b24a63b598c8ab87c33271
Quelldatensatz
uspto-grants-2002_08
Patentnummer
US06437138B1

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