Hydrochloric Acid → HCID 63082745, compound

Temperature

-78 °C

n-Butyllithium (2.66 M solution in hexane, 12.4 mL, 33.0 mmol) was added dropwise to 1-bromo-4-fluorobenzene (5.25 g, 30.0 mmol) in tetrahydrofuran (50 mL) cooled to −78° C., and the reaction mixture was stirred at −78° C. for 30 minutes, mixed with ethyl 2,2,2-trifluoroacetate (4.64 mL, 45 mmol) at −78° C. and then stirred for another 30 minutes while the temperature was gradually raised to room temperature. The reaction mixture was stirred with nitromethane (3.25 mL, 60 mmol) at room temperature for 30 minutes. The resulting reaction mixture was added to 1 M hydrochloric acid (50 mL) and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1 (v/v/)) to give a colorless oil. The colorless oil was dissolved in ethanol (25 mL) and stirred with 10% palladium-carbon (1 g) at room temperature for one day under a hydrogen atmosphere. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure to give the title compound as a colorless solid (4.52 g, yield 68% (three steps)).

1. stirringstirred for another 30 minutes while the temperature
2. temperaturewas gradually raised to room temperature
3. customThe resulting reaction mixture
4. extractionextracted with ethyl acetate
5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1 (v/v/))
8. customto give a colorless oil
9. filtrationThe reaction mixture was filtered through Celite
10. concentrationthe filtrate was concentrated under reduced pressure

ORD record

ord-f2dff2a4b9ec4560b60ef3a03e0298d0

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216999B2