Lithium Chloride → 5-Nitro-2-(trifluoromethyl)phenol

Temperature

120 °C

To a solution of 2-methoxy-4-nitro-1-(trifluoromethyl)benzene (5.0 g, 22.6 mmol) in N,N-dimethylformamide (23 mL) was added lithium chloride (2.40 g, 56.5 mmol), and the mixture was stirred at 120° C. for 2 hr. The reaction temperature was heated to 155° C., and the mixture was further stirred for 12 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (150 mL)/hexane (75 mL), and washed with 1% aqueous citric acid solution (100 mL). The aqueous layer was extracted with ethyl acetate (50 mL)/hexane (25 mL), and the combined organic layer was washed with water (100 mL) and saturated brine (100 mL×2), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=98/2→90/10). The obtained solution was concentrated under reduced pressure to give the title compound (2.22 g, 47%) as a yellow oil.

1. temperatureThe reaction temperature was heated to 155° C.
2. stirringthe mixture was further stirred for 12 hr
3. temperatureThe reaction mixture was cooled to room temperature
4. washwashed with 1% aqueous citric acid solution (100 mL)
5. extractionThe aqueous layer was extracted with ethyl acetate (50 mL)/hexane (25 mL)
6. washthe combined organic layer was washed with water (100 mL) and saturated brine (100 mL×2)
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationThe insoluble material was filtered off
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=98/2→90/10)
11. concentrationThe obtained solution was concentrated under reduced pressure

ORD record

ord-24b307713c83435a9eb02410a659baee

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08344135B2