Diiodomethane → 1-Cyclopropoxy-3,5-difluorobenzene

Temperature

0 °C

To a nitrogen flushed 250 ml round bottom flask equipped with magnetic stirring bar and septa was added 80 ml dichloromethane and Et2Zn (7.18 g, 58.1 mmol). The resulting solution was cooled with ice bath. Trifluoroacetic acid (4.23 ml, 55 mmol) was added by a syringe slowly (septa was opened slightly to release pressure). The reaction mixture was stirred at 0° C. for 10 minutes after addition. Diiodomethane (4.88 ml, 60.4 mmol) was added by a syringe and the resulting reaction mixture was stirred at 0° C. for 10 minutes. A dichloromethane solution of 3,5-difluorophenyl vinyl ether (3.3 g, 21.1 mmol in 10 ml CH2Cl2) was added. The reaction mixture was allowed to warm up to room temperature over 30 minutes, then quenched by addition of 50 ml water and 50 ml 3N HCl. The layers were separated. The aqueous portion was extracted with 50 ml ether. The organics were combined, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel column eluted with hexane to give 3.6 g desired product as light yellow liquid.

1. customTo a nitrogen flushed 250 ml round bottom flask
2. customequipped with magnetic stirring bar
3. temperatureThe resulting solution was cooled with ice bath
4. additionafter addition
5. customthe resulting reaction mixture
6. stirringwas stirred at 0° C. for 10 minutes
7. temperatureto warm up to room temperature over 30 minutes
8. customquenched by addition of 50 ml water and 50 ml 3N HCl
9. customThe layers were separated
10. extractionThe aqueous portion was extracted with 50 ml ether
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated
14. customThe residue was purified on silica gel column
15. washeluted with hexane

ORD record

ord-3351f07234ab4a34b5c3d8c8db229d4e

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304434B2