1,10-Phenanthroline → 6-(Azetidin-3-yloxy)imidazo[1,2-a]pyridine

HRID 2171712Notes

Reaction equation

HRID 2171712 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.[OH:11][CH:12]1[CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13]1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(O)(C(F)(F)F)=O>[Cu](I)I.ClCCl.O.C(Cl)(Cl)Cl.C1(C)C=CC=CC=1>[NH:14]1[CH2:15][CH:12]([O:11][C:2]2[CH:3]=[CH:4][C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[CH:7]=2)[CH2:13]1

Participants

11

Reactant 5

HCID 13181,10-PhenanthrolineHCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylateHCID 27643276-Iodoimidazo(1,2-a)pyridine

Product 1

HCID 683090446-(Azetidin-3-yloxy)imidazo[1,2-a]pyridineYield 60.9%

Reagents, catalysts & solvents 5

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

6-Iodoimidazo[1,2-a]pyridine (400 mg), tert-butyl 3-hydroxyazetidine-1-carboxylate (500 mg), and toluene (2 ml) were mixed, and copper iodide (I) (40 mg), 1,10-phenanthroline (60 mg), and cesium carbonate (1 g) were added thereto, followed by stirring at 100° C. overnight. CHCl3 and water were added to the reaction mixture, and the organic layer was dried over Na2SO4 and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH). The purified product thus obtained was mixed with dichloromethane (5 ml), and TFA (1.5 ml) was added thereto, followed by stirring at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by basic silica gel column chromatography (CHCl3/MeOH) to obtain 6-(azetidin-3-yloxy)imidazo[1,2-a]pyridine (189 mg).

Workup

  1. dry with materialthe organic layer was dried over Na2SO4
  2. concentrationconcentrated under reduced pressure
  3. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)
  4. customThe purified product thus obtained
  5. additionwas added
  6. stirringby stirring at room temperature for 3 hours
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. customthe residue was purified by basic silica gel column chromatography (CHCl3/MeOH)

Sources & evidence

ORD record
ord-e5af155671964c869aceaff5071c4935
Source dataset
uspto-grants-2015_06
Patent number
US09051283B2

Reaction notes

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