Imidazole → Methyl 2-{[tert-butyl(dimethyl)silyl]oxy}-4-{[4-(methoxymethoxy)phenyl]ethynyl}benzoate

HRID 1888743Notes

Reaction equation

HRID 1888743 reaction equation
[OH:1][C:2]1[CH:11]=[C:10](I)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[C:13]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][O:23][CH3:24])=[CH:17][CH:16]=1)#[CH:14].N1C=CN=C1.[C:30]([Si:34](Cl)([CH3:36])[CH3:35])([CH3:33])([CH3:32])[CH3:31]>C(N(CC)CC)C.C(OCC)(=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Si:34]([O:1][C:2]1[CH:11]=[C:10]([C:14]#[C:13][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][O:23][CH3:24])=[CH:17][CH:16]=2)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:36])[CH3:35]

Participants

10

Reactant 4

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 11380407Methyl 4-iodosalicylateHCID 225029951-Ethynyl-4-(methoxymethoxy)benzene

Product 1

HCID 58047299Methyl 2-{[tert-butyl(dimethyl)silyl]oxy}-4-{[4-(methoxymethoxy)phenyl]ethynyl}benzoateYield 84.4%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 2-hydroxy-4-iodobenzoate (6.55 g, 23.6 mmol), 1-ethynyl-4-(methoxymethoxy)benzene (4.58 g, 28.3 mmol) and copper(I) iodide (450 mg, 2.36 mmol) in triethylamine (50 mL) was added bis(triphenylphosphine)palladium(II) chloride (1.66 mg, 2.36 mmol), and the mixture was stirred under an argon stream at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with water, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was dissolved in DMF (30 mL). Imidazole (2.42 g, 35.4 mmol) and tert-butyl(chloro)dimethylsilane (4.27 g, 28.3 mmol) were added thereto, and the mixture was stirred at room temperature for 1.5 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed twice with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1 to 3:2) to give the title compound (8.50 g, yield 84%) as an oil.

Workup

  1. washthe mixture was washed with water
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. dissolutionthe obtained residue was dissolved in DMF (30 mL)
  5. stirringthe mixture was stirred at room temperature for 1.5 hr
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe extract was washed twice with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customthe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1 to 3:2)

Sources & evidence

ORD record
ord-c945331e8ff2433c95fa00b985d9ec22
Source dataset
uspto-grants-2013_08
Patent number
US08501804B2

Reaction notes

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