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

HRID 467532Notes

Reaction equation

[OH-].[K+].[CH2:3]([C:5]1[C:10]([F:11])=[CH:9][C:8]([OH:12])=[C:7]([O:13][CH3:14])[CH:6]=1)[CH3:4].[F:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1F)[C:19]#[N:20]>C(#N)C.CCCCC>[CH2:3]([C:5]1[C:10]([F:11])=[CH:9][C:8]([O:12][C:23]2[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=2[F:15])=[C:7]([O:13][CH3:14])[CH:6]=1)[CH3:4]

Participants

Conditions

Temperature: 85 °C

Procedure

Potassium hydroxide (2.4 g, 43.13 mmol) was added to a solution of 4-ethyl-5-fluoro-2-methoxyphenol (6.1 g, 35.94 mmol) and 3,4-difluorobenzonitrile (5.0 g, 35.94 mmol) in anhydrous acetonitrile (80 mL). The reaction mixture was stirred at 85° C. overnight then concentrated under vacuum. The residue was solubilized in ethyl acetate (300 mL) and diluted by addition of a saturated solution of ammonium chloride (200 mL). The aqueous layer was separated and extracted with ethyl acetate (2×200 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated to dryness to give a brown solid. After trituration in pentane, the title product was obtained as a brown solid (8.10 g, 77%).

Workup

concentrationthen concentrated under vacuum
additiondiluted by addition of a saturated solution of ammonium chloride (200 mL)
customThe aqueous layer was separated
extractionextracted with ethyl acetate (2×200 mL)
dry with materialThe combined organic phases were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated to dryness
customto give a brown solid

Sources & evidence

ORD record: ord-31b62e57cda54c369b9e344647f03fd8
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623865B2

Reaction notes

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