Water → HCID 22262059, compound

To a solution of 3-(1,1,2,2-tetrafluoroethoxy)toluene (7.51 g, 35.6 mmol) in carbon tetrachloride (100 ml) were added N-bromosuccinimide (7.60 g, 42.7 mmol) and 2,2′-azobis(isobutyronitrile) (290 mg, 1.78 mmol), and the mixture was heated under reflux for 4 hrs. After cooling, the reaction solution was filtered, the filtrate was concentrated to give 3-(1,1,2,2-tetrafluoroethoxy)-α-bromotoluene. To a solution of ethyl 3-(6-fluoropyridin-2-yl)-3-oxopropionate (7.51 g, 35.6 mmol) in 1,2-dimethoxyethane (70 ml) was added sodium hydride (60% in oil, 1.42 g, 35.6 mmol) under ice-cooling, and the mixture was stirred at room temperature for 30 min. To the reaction solution was dropwise added a solution of 3-(1,1,2,2-tetrafluoroethoxy)-α-bromotoluene prepared earlier in 1,2-dimethoxyethane (10 ml), and the reaction solution was stirred at room temperature for 1 hr. The reaction solution was poured into water (100 ml), and the mixture was extracted with ethyl acetate (100 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (toluene:hexane=1:1) to give ethyl 3-(6-fluoropyridin-2-yl)-3-oxo-2-((3-(1,1,2,2-tetrafluoroethoxy)phenyl)methyl)propionate (7.74 g, 52%) as a colorless oil.

1. temperaturecooling
2. stirringthe reaction solution was stirred at room temperature for 1 hr
3. extractionthe mixture was extracted with ethyl acetate (100 ml×2)
4. washThe extract was washed with water and saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customevaporated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (toluene:hexane=1:1)

ORD record

ord-8f36b39ad2664230bd1e8922c669bf44

Source dataset

uspto-grants-2006_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06982348B2