Chloromethyl Methyl Ether → Methyl 3-cyano-4-hydroxybenzoate

HRID 385069Notes

Reaction equation

HRID 385069 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([O:7][CH3:8])=[O:6].[Cu](C#N)[C:14]#[N:15].C(=O)([O-])[O-].[K+].[K+].COCCl>CN(C)C=O>[C:14]([C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([O:7][CH3:8])=[O:6])#[N:15]

Participants

6

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 11430Potassium CarbonateHCID 4778958Methyl 3-bromo-4-hydroxybenzoateHCID 178418260HCID 178418260, compound

Product 1

HCID 11769089Methyl 3-cyano-4-hydroxybenzoateYield 22.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

Methyl 3-bromo-4-hydroxybenzoate (37.81 g) was dissolved in N,N-dimethylformamide (250 mL), and copper cyanide (22.03 g) was added to the solution. After stirring the mixture at 150° C. for 16 hours, potassium carbonate (68.00 g) and chloromethyl methyl ether (14.8 mL) were added to the solution under ice cooling, and then the mixture was stirred for 2 hours. The reaction solution was filtered and water was added, and then the reaction mixture was extracted with ethyl acetate. After the operation of adding water to the organic layer, stirring the mixture, filtering the mixture and separating the organic layer was repeated three times, the organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the obtained residue was dissolved in chloroform (30 mL). Trifluoroacetic acid (30 mL) was added to the solution, and then the mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure and the obtained residue was washed with a mixture of n-hexane and ethyl acetate in a mixing ratio of 2:1 to obtain the title compound (6.53 g) as a pale yellow crystal.

Workup

  1. stirringthe mixture was stirred for 2 hours
  2. filtrationThe reaction solution was filtered
  3. additionwater was added
  4. extractionthe reaction mixture was extracted with ethyl acetate
  5. stirringAfter the operation of adding water to the organic layer, stirring the mixture
  6. filtrationfiltering the mixture
  7. customseparating the organic layer
  8. washthe organic layer was washed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. distillationThe solvent was distilled off under reduced pressure
  11. dissolutionthe obtained residue was dissolved in chloroform (30 mL)
  12. additionTrifluoroacetic acid (30 mL) was added to the solution
  13. stirringthe mixture was stirred at room temperature for 2 hours
  14. distillationThe solvent was distilled off under reduced pressure
  15. washthe obtained residue was washed with a mixture of n-hexane and ethyl acetate in a mixing ratio of 2:1

Sources & evidence

ORD record
ord-343776482e974d71913e3c7c4391ee3d
Source dataset
uspto-grants-2013_02
Patent number
US08367843B2

Reaction notes

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