Hydrochloric Acid → 5,6-Dichloro-2-(hexahydro-1H-7a-pyrrolizinyl)furo [3,2-b]pyridine

HRID 611584Notes

Reaction equation

HRID 611584 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([OH:9])=[C:4](I)[N:3]=1.C(N(CC)CC)C.[C:18]([C:20]12[CH2:27][CH2:26][CH2:25][N:24]1[CH2:23][CH2:22][CH2:21]2)#[CH:19].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>[Cl:1][C:2]1[N:3]=[C:4]2[CH:19]=[C:18]([C:20]34[CH2:27][CH2:26][CH2:25][N:24]3[CH2:23][CH2:22][CH2:21]4)[O:9][C:5]2=[CH:6][C:7]=1[Cl:8]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 195976065,6-Dichloro-2-iodopyridin-3-olHCID 195976957a-ethynylhexahydro-1H-pyrrolizine

Product 1

HCID 195975755,6-Dichloro-2-(hexahydro-1H-7a-pyrrolizinyl)furo [3,2-b]pyridineYield 70%

Reagents, catalysts & solvents 3

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

Procedure

2,3-Dichloro-6-iodo-5-pyridinol (163 mg, 0.56 mmol) from example 25a, copper(I) iodide (20 mg, 0.10 mmol), bis(triphenylphosphine)palladium(II) chloride (20 mg, 0.030 mmol) and triethylamine (176 mL, 0.67 mmol) were combined and allowed to stir for 1 hour at ambient temperature. 7a-ethynyl-hexahydro-1H-pyrrolizine (91 mg, 0.67 mmol) in DMF (1.0 mL) was added to the reaction mixture which was then heated to 60° C. for 18 hours. After cooling to ambient temperature, 2 N aqueous HCl was added and the mixture was washed with Et2O (2×), basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The CH2Cl2 phases were combined, dried (MgSO4), concentrated and the residue was chromatographed (silica gel; EtOAc/hexane, 1:3) to afford a white solid (116 mg, 70%): 1H NMR (CDCl3, 300 MHz) δ 1.83-1.97 (m, 6H), 2.20-2.31 (m, 2H), 2.67-2.77 (m, 2H), 3.18-3.25 (m, 2H), 6.71 (s, 1H), 7.78 (s, 1H); MS (CI/NH3) m/z: 297 (M+H)+.

Workup

  1. temperaturewas then heated to 60° C. for 18 hours
  2. temperatureAfter cooling to ambient temperature
  3. washthe mixture was washed with Et2O (2×)
  4. extractionextracted with CH2Cl2 (2×)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customthe residue was chromatographed (silica gel; EtOAc/hexane, 1:3)

Sources & evidence

ORD record
ord-b93c26e4ab2740ad95655d576f9567bd
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Reaction notes

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