Reaction #2028870

Reaction equation

acetyl chloride

Aluminum chloride

2-fluoroanisole

→

material

Yield 92.0%

3′-fluoro-4′-methoxyacetophenone

Yield 92.0%

Solvents

chloroform

Conditions

Workup

1. 1
   Otherfitted with a mechanical stirrer
2. 2
   Temperaturecooled by means of an ice bath
3. 3
   Temperaturemaintaining the temperature between 5°-10° C
4. 4
   OtherThe resultant layers were separated
5. 5
   Extractionthe aqueous layer was extracted with dichloromethane (2×250 mL)
6. 6
   WashThe combined organic layers were washed with water (2×150 mL)
7. 7
   Dryingdried over anhydrous MgSO4
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated in vacuo to a volume of 300 mL
10. 10
    workup.ADDITIONHexanes were added
11. 11
    Othera white solid formed which
12. 12
    Otherwas isolated by filtration and air
13. 13
    Otherdried
14. 14
    OtherThis material was recrystallized from a mixture of dichloromethane and hexanes

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-fluoroanisole (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 92°-94° C.; 1H NMR (DMSO-d6) 7.8 (m, 2H), 7.3 (t, 1H), 3.9 (s, 3H), 2.5 (s, 3H).

Source