Dimethylformamide → 5'-Ethoxy-2'-fluorobiphenyl-2-carbonitrile

HRID 705052

Reaction equation

HRID 705052 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:13])=[C:8](B(O)O)[CH:9]=1)[CH3:2].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C)C=O.Cl[C:28]1[CH:35]=[CH:34][CH:33]=[CH:32][C:29]=1[C:30]#[N:31]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:13])=[C:8]([C:28]2[C:29]([C:30]#[N:31])=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:9]=1)[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 133912-ChlorobenzonitrileHCID 62657Potassium Phosphate, TribasicHCID 162174685-Ethoxy-2-fluorophenylboronic Acid (contains varying amounts of Anhydride)

Product 1

HCID 711866555'-Ethoxy-2'-fluorobiphenyl-2-carbonitrileYield 76%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

Under argon, 5-ethoxy-2-fluorophenylboronic acid (300 mg, 1.63 mmol), potassium phosphate (433 mg, 2.04 mmol) and tetrakis(triphenylphosphine)palladium(0) (57 mg, 0.05 mmol) were dissolved in abs. N,N-dimethylformamide (8 ml), and the mixture was stirred at room temperature for 5 minutes. 2-Chlorobenzonitrile (112 mg, 0.82 mmol) was then added, and the reaction mixture was stirred at 160° C. for 4 h. After cooling to room temperature, water (>100 ml) was added and the aqueous phase was repeatedly extracted thoroughly with ethyl acetate. The combined organic phases were dried over magnesium sulphate, filtered off and concentrated under reduced pressure. Purification of the residue that remained by column chromatography (gradient ethyl acetate/n-heptane) gave 5′-ethoxy-2′-fluorobiphenyl-2-carbonitrile (150 mg, 76% of theory) in the form of a colourless solid. 5′-Ethoxy-2′-fluorobiphenyl-2-carbonitrile (150 mg, 0.62 mmol) was then dissolved in methanol (5 ml), finely powdered potassium hydroxide (174 mg, 3.10 mmol) was added and the mixture was stirred under reflux conditions for 2 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure, water was added and the resulting precipitated solid was filtered off and dried. This gave 2-ethoxyphenanthridin-6(5H)-one (72 mg, 46% of theory) as a colourless solid. 1H-NMR (400 MHz, d6-DMSO δ, ppm) 11.58 (br. s, 1H, NH), 8.56 (d, 1H), 8.32 (d, 1H), 7.86 (d, 1H), 7.82 (dd, 1H), 7.64 (dd, 1H), 7.29 (d, 1H), 7.13 (dd, 1H), 4.17 (q, 2H), 1.39 (t, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe aqueous phase was repeatedly extracted thoroughly with ethyl acetate
  3. dry with materialThe combined organic phases were dried over magnesium sulphate
  4. filtrationfiltered off
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the residue

Sources & evidence

ORD record
ord-7f45648b4cc54c46847dce4a22f68f3e
Source dataset
uspto-grants-2015_11
Patent number
US09173395B2

Linked notes

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