Ethanol → 3'-Chloro-4'-methoxyacetophenone

HRID 1781448Notes

Reaction equation

HRID 1781448 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[CH2:5]([OH:7])[CH3:6].C(Cl)(=O)C.[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[O:19][CH3:20]>C(Cl)(Cl)Cl.O>[CH3:6][C:5]([C:17]1[CH:16]=[CH:15][C:14]([O:19][CH3:20])=[C:13]([Cl:12])[CH:18]=1)=[O:7]

Participants

7

Reactant 4

HCID 702EthanolHCID 6367Acetyl chlorideHCID 130112-ChloroanisoleHCID 6451240Aluminum(III) Chloride

Product 1

HCID 5208573'-Chloro-4'-methoxyacetophenoneYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent2×

Procedure

A 5 L round bottomed flask equipped with mechanical stirrer, reflux condenser, constant pressure addition funnel and nitrogen inlet was charged with anhydrous aluminum chloride (281 g, 2.104 mol) and 1 L of ethanol-free chloroform. The solution was maintained at 0° C. with an ice bath while a solution of acetyl chloride (162 g, 2.28 mol) in 300 mL of chloroform was added from the addition funnel over 25 minutes. To this solution was added 2-chloroanisole (250 g, 1.75 mol) in 250 mL of chloroform over 1 hour. The solution was stirred at room temperature for 16 hours and the contents of the flask were poured into a mixture of ice and water. The phases were separated and the aqueous phase extracted with dichloromethane and combined with the original organic phase, dried over anhydrous MgSO4, filtered and concentrated in vacuo to afford a solid that was crystallized from dichloromethane/hexane to give 3-chloro-4-methoxyacetophenone (246 g, 76%) that was used directly in the next step without further purification.

Workup

  1. customA 5 L round bottomed flask equipped with mechanical stirrer
  2. temperaturereflux
  3. additioncondenser, constant pressure addition funnel and nitrogen inlet
  4. additionwas added from the addition funnel over 25 minutes
  5. customThe phases were separated
  6. extractionthe aqueous phase extracted with dichloromethane
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto afford a solid
  11. customthat was crystallized from dichloromethane/hexane

Sources & evidence

ORD record
ord-910b64cf7107460095428f271d09d2fa
Source dataset
uspto-grants-1997_05
Patent number
US05633272

Reaction notes

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