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

HRID 611576

Reaction equation

HRID 611576 reaction equation
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

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

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)+.

Workup

  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.

Sources & evidence

ORD record
ord-665654d203c64b408d7ffe9d56cf0168
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Linked notes

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