8-Hydroxyquinoline → HCID 86723571, compound

HRID 2170918Notes

Reaction equation

HRID 2170918 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, compoundYield 295.4%

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 (702 mg, 42% yield).

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-fb2f3765e55148958998835de57f991c
Source dataset
uspto-grants-2015_06
Patent number
US09051313B2

Reaction notes

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