Potassium Iodide → 5-Iodo-1,2,3,4-tetrahydro-1,8-naphthyridine

HRID 1499474

Reaction equation

HRID 1499474 reaction equation
Cl[CH2:2][CH2:3][CH2:4][C:5]1[C:6](F)=[N:7][CH:8]=[CH:9][C:10]=1[I:11].[NH4+:13].[OH-].C([O-])(=O)C.[NH4+].[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CCOC(C)=O.CN(C=O)C>[I:11][C:10]1[CH:9]=[CH:8][N:7]=[C:6]2[C:5]=1[CH2:4][CH2:3][CH2:2][NH:13]2

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 517165Ammonium AcetateHCID 236572333-(3-Chloropropyl)-2-fluoro-4-iodopyridine

Product 1

HCID 577562535-Iodo-1,2,3,4-tetrahydro-1,8-naphthyridineYield 69%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-(3-chloropropyl)-2-fluoro-4-iodopyridine (5.0 g, 17 mmol), NH4OH (100 mL, 800 mmol), ammonium acetate (18 g, 230 mmol), potassium iodide (5.5 g, 33 mmol), potassium carbonate (12 g, 87 mmol) and DMF (26 mL) was heated at 60° C. for 8 h. The mixture allowed to cool, and diluted with EtOAc. The layers were separated and the organic layer was washed with brine, dried with MgSO4, then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using CombiFlash® apparatus, eluting with 0 to 50% EtOAc in hexanes, to give the sub-title compound (3.0 g, 69% yield). LCMS calc. for C8H10IN2(M+H)+: m/z=261.0. Found: 261.1.

Workup

  1. temperatureto cool
  2. customThe layers were separated
  3. washthe organic layer was washed with brine
  4. dry with materialdried with MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel using CombiFlash® apparatus
  7. washeluting with 0 to 50% EtOAc in hexanes

Sources & evidence

ORD record
ord-78e87c30a9734fc689d5da3dea89c409
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Linked notes

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