Acetyl chloride → 1-(4-Hydroxy-2-methoxy-5-methylphenyl)ethanone

HRID 852426Notes

Reaction equation

HRID 852426 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[Al+3].[Cl-].[Cl-].[Cl-].[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([CH3:18])=[C:15]([OH:17])[CH:16]=1>ClCCCl.CO.C1COCC1.[Li+].[OH-]>[OH:17][C:15]1[C:14]([CH3:18])=[CH:13][C:12]([C:1](=[O:3])[CH3:2])=[C:11]([O:10][CH3:9])[CH:16]=1

Participants

8

Reactant 3

HCID 6367Acetyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 109535825-Methoxy-2-methylphenol

Product 1

HCID 674025401-(4-Hydroxy-2-methoxy-5-methylphenyl)ethanoneYield 30%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolvent2×HCID 887MethanolSolventHCID 3939Lithium HydroxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

1.16 ml (16 mmol) Acetylchloride were added within 5 min to a ice cooled suspension of 2.4 g (16.4 mmol) AlCl3 in 5 ml 1,2-dichloroethane under an argon atmosphere. A solution of 1.13 g (8.2 mmol) 5-methoxy-2-methyl-phenol (PCT Int. Appl. WO 2003/084916 A2) in 2.4 ml 1,2-dichloroethane was added within 5 min. The mixture was naturally warmed to ambient temperature, poured after 4 h onto ice water and extracted twice with dichloromethane. The combined extracts were washed with ice water/0.5 M NaOH solution 1/1 and brine and dried over sodium sulfate. Removal of the solvent under reduced pressure gave a yellow oil which was dissolved in a mixture of 3.5 ml methanol, 7 ml THF and 7 ml 1 M LiOH solution. The solution was stirred for 30 min at ambient temperature and the solvent was partially removed under reduced pressure. Ice water/1 M HCl solution 1/1 was added and the solution was extracted twice with ethyl acetate. The combined extracts were washed with brine and dried over sodium sulfate. Evaporation of the solvent left a yellow solid which was crystallized from dichloromethane/methanol/heptane to yield 441 mg (2.45 mmol, 30%) of the title compound as colorless crystals.

Workup

  1. temperaturecooled
  2. additionpoured after 4 h onto ice water
  3. extractionextracted twice with dichloromethane
  4. washThe combined extracts were washed with ice water/0.5 M NaOH solution 1/1 and brine
  5. dry with materialdried over sodium sulfate
  6. customRemoval of the solvent under reduced pressure
  7. customgave a yellow oil which
  8. customthe solvent was partially removed under reduced pressure
  9. additionIce water/1 M HCl solution 1/1 was added
  10. extractionthe solution was extracted twice with ethyl acetate
  11. washThe combined extracts were washed with brine
  12. dry with materialdried over sodium sulfate
  13. customEvaporation of the solvent
  14. waitleft a yellow solid which
  15. customwas crystallized from dichloromethane/methanol/heptane

Sources & evidence

ORD record
ord-7abb835af5fb4285a4f6e5125f275e2e
Source dataset
uspto-grants-2007_08
Patent number
US07253192B2

Reaction notes

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