Hydrochloric Acid → 2-(Hexahydro-1H-7a-pyrrolizinyl)furo[3,2-b]pyridine

HRID 611576

Reaktionsgleichung

Reaktionsgleichung von HRID 611576
I[C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[C:16]([C:18]12[CH2:25][CH2:24][CH2:23][N:22]1[CH2:21][CH2:20][CH2:19]2)#[CH:17].Cl>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:19]1[C:18]2([C:16]3[O:8][C:7]4[C:2](=[N:3][CH:4]=[CH:5][CH:6]=4)[CH:17]=3)[N:22]([CH2:23][CH2:24][CH2:25]2)[CH2:21][CH2:20]1

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 971792-Iodopyridin-3-olHCID 195976957a-ethynylhexahydro-1H-pyrrolizine

Produkt 1

HCID 195976462-(Hexahydro-1H-7a-pyrrolizinyl)furo[3,2-b]pyridine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

2-Iodo-3-pyridinol (902 mg, 4.1 mmol), copper(I) iodide (116 mg, 0.61 mmol), bis(triphenylphosphine)palladium(II) chloride (119 mg, 0.17 mmol) and triethylamine (570 mL, 4.1 mmol) were combined in DMF (4.5 mL) and stirred for one hour. 7a-Ethynyl-hexahydro-1H-pyrrolizine(460 mg, 3.4 mmol) in DMF (1.2 mL) was added dropwise and the mixture was heated at 60° C. for 18 h. The reaction mixture was allowed to cool to ambient temperature and 2 N aqueous HCl was added. The heterogeneous mixture was washed with Et2O (2×), basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The CH2Cl2 extracts were combined, dried (MgSO4) concentrated and chromatographed (silica gel; CHCl3 /MeOH, 96:4) to afford an amber oil which solidified upon storage at -20° C. (405 mg, 52%): mp 39-41° C.; 1H NMR (CDCl3, 300 MHz) δ 1.86-1.97 (m, 6H), 2.24-2.34 (m, 2H), 2.68-2.76 (m, 2H), 3.21-3.28 (m, 2H), 6.77 (s, 1H), 7.12 (dd, J=8.5, 5 Hz, 1H), 7.65 (d, J=8.5 Hz, 1H), 8.46 (d, J=5 Hz, 1H); MS (CI/NH3) m/z: 229 (M+H)+.

Aufarbeitung

  1. temperatureto cool to ambient temperature
  2. washThe heterogeneous mixture was washed with Et2O (2×)
  3. extractionextracted with CH2Cl2 (2×)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customchromatographed (silica gel; CHCl3 /MeOH, 96:4)
  7. customto afford an amber oil which
  8. customsolidified upon storage at -20° C.

Quellen und Nachweise

ORD-Eintrag
ord-665654d203c64b408d7ffe9d56cf0168
Quelldatensatz
uspto-grants-1999_12
Patentnummer
US06001849

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