Potassium Hydroxide → 4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzonitrile

HRID 467525Notes

Reaction equation

[CH2:1]([C:3]1[C:8]([F:9])=[CH:7][C:6]([OH:10])=[C:5]([O:11][CH3:12])[CH:4]=1)[CH3:2].[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=1F)[C:17]#[N:18].[OH-].[K+]>C(#N)C>[CH2:1]([C:3]1[C:8]([F:9])=[CH:7][C:6]([O:10][C:21]2[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=2[F:13])=[C:5]([O:11][CH3:12])[CH:4]=1)[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

A suspension of 4-ethyl-5-fluoro-2-methoxyphenol (1 g, 5.87 mmol), 3,4-difluorobenzonitrile (899 mg, 6.46 mmol) and potassium hydroxide (395 mg, 7.04 mmol) in anhydrous acetonitrile (35 mL) under argon was stirred at 80° C. overnight. The reaction mixture was concentrated under vacuum and diluted with ethyl acetate and a saturated aqueous solution of ammonium chloride. The aqueous layer was separated and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtrated and concentrated in vacuo to give a brown oil (1.6 g). The crude product was purified by flash chromatography on silica gel, using cyclohexane/ethyl acetate (9:1) as eluent. The title product was obtained as a colourless oil that crystallized slowly (1.42 g, 84%).

Workup

concentrationThe reaction mixture was concentrated under vacuum
additiondiluted with ethyl acetate
customThe aqueous layer was separated
extractionextracted twice with ethyl acetate
dry with materialThe combined organic phases were dried over sodium sulfate
filtrationfiltrated
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-8bbfbe9046084723a9c4e940c89c961d
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623865B2

Reaction notes

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