1,10-Phenanthroline → Methyl 3-({6-[(3-chloropyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoate

HRID 1843692Notes

Reaction equation

HRID 1843692 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH2:10][O:11][C:12]3[CH:13]=[C:14]([CH:19]=[CH:20][CH:21]=3)[C:15]([O:17][CH3:18])=[O:16])[N:7]([CH3:22])[C:6]=2[CH:23]=1.[Cl:24][C:25]1[C:26](F)=[N:27][CH:28]=[CH:29][CH:30]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl-].[NH4+]>CN(C=O)C.[Cu](I)I>[Cl:24][C:25]1[C:26]([O:1][C:2]2[CH:3]=[CH:4][C:5]3[N:9]=[C:8]([CH2:10][O:11][C:12]4[CH:13]=[C:14]([CH:19]=[CH:20][CH:21]=4)[C:15]([O:17][CH3:18])=[O:16])[N:7]([CH3:22])[C:6]=3[CH:23]=2)=[N:27][CH:28]=[CH:29][CH:30]=1

Participants

8

Reactant 5

HCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 27628183-Chloro-2-fluoropyridineHCID 56933238Methyl 3-[(6-hydroxy-1-methyl-1H-benzimidazol-2-yl)methoxy]benzoate

Product 1

HCID 66705784Methyl 3-({6-[(3-chloropyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoateYield 58%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of methyl 3-[(6-hydroxy-1-methyl-1H-benzimidazol-2-yl)methoxy]benzoate produced in Example (1e) (3.12 g, 10 mmol), 3-chloro-2-fluoropyridine (1.45 g, 11 mmol), copper iodide (0.19 g, 1.0 mmol), 1,10-phenanthroline (0.18 g, 1.0 mmol) and cesium carbonate (9.77 g, 30 mmol) in DMF (50 mL) was stirred in a nitrogen atmosphere at 80° C. for two hours. After leaving to cool, a saturated ammonium chloride aqueous solution (200 mL) was added to the reaction mixture, followed by extraction with ethyl acetate (200 mL). Then, the organic layer was washed with water (200 mL) twice and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (methylene chloride/methanol, 95:5) to obtain the title compound (2.46 g, 58%) as a white solid.

Workup

  1. customAfter leaving
  2. temperatureto cool
  3. extractionfollowed by extraction with ethyl acetate (200 mL)
  4. washThen, the organic layer was washed with water (200 mL) twice
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationAfter concentration under reduced pressure
  7. customthe residue was purified by silica gel chromatography (methylene chloride/methanol, 95:5)

Sources & evidence

ORD record
ord-ae6704c2ceba456db200cc789dc6e48d
Source dataset
uspto-grants-2015_02
Patent number
US08946264B2

Reaction notes

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