Citric Acid → 1-Chloro-2-methoxy-4-methylbenzene

HRID 1874758Notes

Reaction equation

HRID 1874758 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][C:5]=1[OH:11].CI.[C:14](O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.CCOC(C)=O>[CH3:14][O:11][C:5]1[CH:6]=[C:7]([CH3:10])[CH:8]=[CH:9][C:4]=1[Cl:3]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 6328Methyl iodideHCID 120082-Chloro-5-methylphenolHCID 24758Sodium hydride

Product 1

HCID 993521-Chloro-2-methoxy-4-methylbenzeneYield 100%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (60% dispersion, 3.0 g, 77 mmol) was added in three portions to a solution of 2-chloro-5-methylphenol (10.0 g, 70.1 mmol) in DMF (100 mL) at 0° C. under nitrogen. Methyl iodide (5.0 mL, 77 mmol) was added and the solution was warmed to RT. After 1 h, 10% aqueous citric acid (200 mL) and EtOAc (1.0 L) were added. The layers were separated and the aqueuos layer was extracted with EtOAc. The organic layer was washed with saturated NaHCO3 and brine, dried over Na2SO4, filtered and evaporated. Purification was accomplished by column chromatography (hexane/EtOAc) to afford the title compound (12 g, 100%).

Workup

  1. customThe layers were separated
  2. extractionthe aqueuos layer was extracted with EtOAc
  3. washThe organic layer was washed with saturated NaHCO3 and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customPurification

Sources & evidence

ORD record
ord-7e0f03dc8cd94ede8f01c9fbdfd7517f
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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