Acetyl chloride → 1-(3-Fluoro-4-methoxyphenyl)ethan-1-one

HRID 2084702Notes

Reaction equation

HRID 2084702 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[C:5](Cl)(=[O:7])[CH3:6].[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[O:16][CH3:17]>C(Cl)(Cl)Cl>[F:9][C:10]1[CH:15]=[C:14]([C:5](=[O:7])[CH3:6])[CH:13]=[CH:12][C:11]=1[O:16][CH3:17]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 675762-FluoroanisoleHCID 6451240Aluminum(III) Chloride

Product 1

HCID 968281-(3-Fluoro-4-methoxyphenyl)ethan-1-oneYield 92%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
7.5 °C

Procedure

Aluminum chloride (80.0 g, 0.6 mol) and chloroform (750 mL) were placed in a 2 L three-necked round bottom flask fitted with a mechanical stirrer and cooled by means of an ice bath. To the stirred solution acetyl chloride (51.0 g, 0.65 mol) was added dropwise, maintaining the temperature between 5-10° C. The mixture was stirred for 10 minutes at 5° C. before the dropwise addition at 5-10° C. of 2-fluoroanisol (62.6 g 0.5 mol). The mixture was stirred at 0-10° C. for 1 hour and poured into ice (1 L). The resultant layers were separated and the aqueous layer was extracted with dichloromethane (2×250 mL). The combined organic layers were washed with water (2×150 mL), dried over anhydrous MgSO4, filtered and concentrated in vacuo to a volume of 300 mL. Hexanes were added and a white solid formed which was isolated by filtration and air dried. This material was recrystallized from a mixture of dichloromethane and hexanes to afford (77.2 g, 92%) of material suitable for use in the next step: mp 93-94° C.; 1H NMR (DMSO-d6) 7.8 (m, 2H), 7.3 (t, 1H), 3.9 (s, 3H), 2.5 (s, 3H).

Workup

  1. customfitted with a mechanical stirrer
  2. temperaturecooled by means of an ice bath
  3. customThe resultant layers were separated
  4. extractionthe aqueous layer was extracted with dichloromethane (2×250 mL)
  5. washThe combined organic layers were washed with water (2×150 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to a volume of 300 mL
  9. additionHexanes were added
  10. customa white solid formed which
  11. customwas isolated by filtration and air
  12. customdried
  13. customThis material was recrystallized from a mixture of dichloromethane and hexanes

Sources & evidence

ORD record
ord-4c4c929edfc74514864b4be74f38bee6
Source dataset
uspto-grants-2004_04
Patent number
US06716991B1

Reaction notes

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