8-Hydroxyquinoline → HCID 86723571, compound

HRID 1754280Notes

Reaction equation

HRID 1754280 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([F:9])=[CH:4][N:3]=1.[CH:10]1([C:13]2[N:14]=[CH:15][NH:16][CH:17]=2)[CH2:12][CH2:11]1.OC1C=CC=C2C=1N=CC=C2.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)CCC>[Cl:1][C:2]1[CH:7]=[C:6]([N:16]2[CH:17]=[C:13]([CH:10]3[CH2:12][CH2:11]3)[N:14]=[CH:15]2)[C:5]([F:9])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 248204952-Chloro-5-fluoro-4-iodopyridineHCID 178420870HCID 178420870, compound

Product 1

HCID 86723571HCID 86723571, compound

Reagents, catalysts & solvents 1

HCID 8008ButyronitrileSolvent

Procedure

A suspension 2-chloro-5-fluoro-4-iodopyridine (1.8 g, 1.00 mmol), 4-cyclopropyl imidazole (982 mg, 9.10 mmol), Cu2O (100 mg, 0.700 mmol), 8-hydroxyquinoline (152 mg, 1.05 mmol), cesium carbonate (4.60 g, 14.0 mmol), and PEG-3350 (1.4 g) in butyronitrile (50 mL) was heated at 65° C. for 16 hours. The reaction mixture was filtered through Celite, concentrated and the residue was partitioned between dichlormethane and water. The layers were separated and the aqueous layer washed twice with dichloromethane. The combined organic layers were dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (15→60% EtOAc in hexanes) to afford 2-chloro-4-(4-cyclopropyl-1H-imidazol-1-yl)-5-fluoropyridine.

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. concentrationconcentrated
  3. customthe residue was partitioned between dichlormethane and water
  4. customThe layers were separated
  5. washthe aqueous layer washed twice with dichloromethane
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography (15→60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-20f84aeb31374ff8bf73ba6b287e70c6
Source dataset
uspto-grants-2015_10
Patent number
US09169243B2

Reaction notes

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