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

Acetyl chloride (51.0 g, 0.65 mol) was added dropwise to a stirred solution of aluminum chloride (80.0 g, 0.6 mol) and chloroform (750 mL), maintaining the temperature between 5–10° C. The mixture was stirred for 10 minutes at 5° C. before the dropwise addition 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 material suitable for use in the next step (77.2 g, 92%): mp 92–94° C.

1. temperaturemaintaining the temperature between 5–10° C
2. customThe resultant layers were separated
3. extractionthe aqueous layer was extracted with dichloromethane (2×250 mL)
4. washThe combined organic layers were washed with water (2×150 mL)
5. dry with materialdried over anhydrous MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo to a volume of 300 mL
8. additionHexanes were added
9. customa white solid formed which
10. customwas isolated by filtration and air
11. customdried
12. customThis material was recrystallized from a mixture of dichloromethane and hexanes
13. customto afford material suitable for use in the next step (77.2 g, 92%)

ORD record

ord-380f2953c36b4374a7bd9e4bf4bace6c

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07141599B2