Ethyl Acetate → 2-(1-Methyl-1h-imidazol-4-yl)-4-[(6-nitro-3-pyridinyl)oxy]pyridine

HRID 2278910Notes

Reaction equation

HRID 2278910 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[CH3:18][N:19]1[CH:23]=[C:22]([Sn](CCCC)(CCCC)CCCC)[N:21]=[CH:20]1.[F-].[K+].CCOC(C)=O>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:18][N:19]1[CH:23]=[C:22]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)[N:21]=[CH:20]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 522689Potassium FluorideHCID 219011411-Methyl-4-(tributylstannyl)-1H-imidazoleHCID 593227792-Chloro-4-((6-nitropyridin-3-yl)oxy)pyridine

Product 1

HCID 904032142-(1-Methyl-1h-imidazol-4-yl)-4-[(6-nitro-3-pyridinyl)oxy]pyridineYield 91%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of Example A1 (1.5 g, 5.96 mmol), N-methyl-4-(tributylstannyl)imidazole (3.32 g, 8.94 mmol) and Pd(PPh3)4 (0.344 g, 0.298 mmol) in toluene (30 mL) sparged with Ar and heated at 110° C. overnight. The mixture was cooled to RT, treated with 10% KF and EtOAc, stirred at RT for 2 h, the solids removed via filtration through diatomaceous earth and washed with 5% MeOH/DCM. The layers of the filtrate were separated and the organic layer was washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was washed with a small amount of Et2O and dried to afford 2-(1-methyl-1H-imidazol-4-yl)-4-((6-nitropyridin-3-yl)oxy)pyridine (1.61 g, 91%). MS (ESI) m/z: 298.1 (M+H+).

Workup

  1. temperatureThe mixture was cooled to RT
  2. customthe solids removed via filtration through diatomaceous earth
  3. washwashed with 5% MeOH/DCM
  4. customThe layers of the filtrate were separated
  5. washthe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (MeOH/DCM)
  9. washThe material was washed with a small amount of Et2O
  10. customdried

Sources & evidence

ORD record
ord-9b5513976e7948a1a72db9239f211e8f
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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