18-Crown-6 → HCID 23001279, compound

Temperature

140 °C

A mixture of potassium fluoride on alumina (40% w/w, Aldrich, 11 g), 2-fluorobenzonitrile (6.0 ml, 56 mmol), 3-trifluoromethoxyphenol (10 g, 56 mmol), and 18-crown-6 (1.48 g, 5.6 mmol) in dimethylsulphoxide (40 ml) was heated to 140° C. for 20 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (300 ml). The solid was filtered off through a plug of celite. The solution was washed with a mixture of water (100 ml) and brine (100 ml). The aqueous phase was extracted with ethyl acetate (2×50 ml). The combined organic layers were washed with water (100 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (200 g), using ethyl acetate/heptane (1:3) as eluent, to give 9.80 g of 2-(3-(difluoromethoxy)phenoxy)benzonitrile.

1. temperatureThe reaction mixture was cooled to room temperature
2. filtrationThe solid was filtered off through a plug of celite
3. washThe solution was washed with a mixture of water (100 ml) and brine (100 ml)
4. extractionThe aqueous phase was extracted with ethyl acetate (2×50 ml)
5. washThe combined organic layers were washed with water (100 ml)
6. dry with materialdried over magnesium sulphate
7. customThe solvent was removed in vacuo
8. customThe crude product was purified by flash chromatography on silica (200 g)

ORD record

ord-c4845bfbd7ef42639df8fb595570e36f

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06610721B2