Sodium Hydroxide → 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde

HRID 2076268Notes

Reaction equation

HRID 2076268 reaction equation
N1CCCC1.[H-].COCCO[Al+]OCCOC.[Na+].[H-].CC(C)([O-])C.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:34]=[CH:35][C:36]=1[N:37]1[CH:41]=[C:40]([CH3:42])[N:39]=[CH:38]1)[C:30](OC)=[O:31].[OH-].[Na+]>C(OCC)(=O)C.C1COCC1.C1(C)C=CC=CC=1>[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:34]=[CH:35][C:36]=1[N:37]1[CH:41]=[C:40]([CH3:42])[N:39]=[CH:38]1)[CH:30]=[O:31]

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 31268PyrrolidineHCID 45749132-Methylpropan-2-olateHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 27282443Methyl 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzoate

Product 1

HCID 272824453-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehydeYield 40.4%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent4×HCID 8857Ethyl AcetateSolvent

Procedure

A THF (45 mL) solution of pyrrolidine (18 mL) was added dropwise to a THF (60 mL) solution of sodium bis(2-methoxyethoxy)aluminium hydride (a 65% toluene solution, 56 mL) at −5° C. or lower over a period of 15 minutes. The reaction liquid was stirred at room temperature for one hour, to which a THF (15 mL) suspension of tertiary-butoxide (2.10 g) was then dropwise added at room temperature, followed by stirring the reaction liquid for 15 minutes. The reaction liquid was added dropwise to a THF (50 mL) solution of methyl 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzoate (20 g) under cooling with ice over a period of 30 minutes. The reaction liquid was stirred at room temperature for 2 hours, to which a 5N sodium hydroxide aqueous solution (150 mL) was then added dropwise. Ethyl acetate was added to the reaction liquid to separate an organic layer. The organic layer was washed with a saturated ammonium chloride aqueous solution and saturated saline in that order. The organic layer was dried with anhydrous magnesium sulfate and filtered on a silica gel pad, followed by concentrating the filtrate under reduced pressure. The residue was diluted with ethyl acetate, followed by collecting the precipitated solid by filtration. The resultant solid was air-dried overnight to provide 7.10 g of the title compound. In addition, the crystallizing mother liquor was concentrated under reduced pressure, followed by purifying the residue using silica gel column chromatography (elution solvent: a heptane-ethyl acetate-2-propanol system) to provide 2.65 g of the title compound.

Workup

  1. customThe reaction liquid
  2. additionwas then dropwise added at room temperature
  3. stirringby stirring
  4. customthe reaction liquid for 15 minutes
  5. customThe reaction liquid
  6. temperatureunder cooling with ice over a period of 30 minutes
  7. customThe reaction liquid
  8. additionwas then added dropwise
  9. customto separate an organic layer
  10. washThe organic layer was washed with a saturated ammonium chloride aqueous solution and saturated saline in that order
  11. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  12. filtrationfiltered on a silica gel pad
  13. concentrationby concentrating the filtrate under reduced pressure
  14. additionThe residue was diluted with ethyl acetate
  15. customby collecting the precipitated solid
  16. filtrationby filtration
  17. customThe resultant solid was air-dried overnight

Sources & evidence

ORD record
ord-4b2d9813c5784ead957042d616978854
Source dataset
uspto-grants-2011_04
Patent number
US07923563B2

Reaction notes

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