Toluene → HCID 66995294, compound

HRID 562919Notes

Reaction equation

HRID 562919 reaction equation
[C:1]1(C)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:8]([C:10]1[CH:11]=[C:12]([C:24]2[CH:25]=[C:26]([CH:31]=[CH:32][N:33]=2)[C:27]([O:29][CH3:30])=[O:28])[CH:13]=[CH:14][C:15]=1OS(C(F)(F)F)(=O)=O)#[N:9].C1(B(O)O)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>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>[C:8]([C:10]1[CH:11]=[C:12]([C:24]2[CH:25]=[C:26]([CH:31]=[CH:32][N:33]=2)[C:27]([O:29][CH3:30])=[O:28])[CH:13]=[CH:14][C:15]=1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)#[N:9]

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 86616562Methyl 2-(3-cyano-4-([(trifluoromethyl)sulfonyl]oxy)phenyl)isonicotinate

Product 1

HCID 66995294HCID 66995294, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

87 mg of tetrakis(triphenylphosphine)palladium was added to a toluene (25 ml) suspension of 966 mg of methyl 2-(3-cyano-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)isonicotinate, 610 mg of phenylboronic acid and 518 mg of potassium carbonate, followed by heating at 100° C. in an argon atmosphere for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5 to 70:30) to obtain 758 mg of methyl 2-(2-cyanobiphenyl-4-yl)isonicotinate. (2) 758 mg of this compound was dissolved in a mixture of 10 ml of methanol and 10 ml of THF, and 7.2 ml of aqueous 1 M sodium hydroxide solution was added thereto, followed by heating at 60° C. for 13 hours. The reaction mixture was cooled to room temperature, neutralized with 1 M hydrochloric acid, and concentrated under reduced pressure. The residue was recrystallized from a mixture of ethanol and water to obtain 472 mg of 2-(2-cyanobiphenyl-4-yl)isonicotinic acid. (3) 414 mg of this compound was dissolved in 15 ml of ethanol, and 1.5 ml of aqueous 1 M sodium hydroxide solution was added thereto, followed by stirring at room temperature for 30 minutes. The reaction solution was concentrated under reduced pressure to obtain 430 mg of sodium 2-(2-cyanobiphenyl-4-yl)isonicotinate.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with brine
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5 to 70:30)

Sources & evidence

ORD record
ord-b58b4afc178e4201949ad3ca4e0f8c8a
Source dataset
uspto-grants-2011_11
Patent number
US08067446B2

Reaction notes

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