Toluene → HCID 57668051, compound

HRID 2191648Notes

Reaction equation

HRID 2191648 reaction equation
C1(C)C=CC=CC=1.Br[C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[C:11]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH:10]=1.[S:27]1[CH:31]=[CH:30][CH:29]=[C:28]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>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(O)C>[F:26][C:23]1[CH:24]=[CH:25][C:20]([NH:19][C:11]2[CH:10]=[C:9]([C:28]3[S:27][CH:31]=[CH:30][CH:29]=3)[CH:18]=[CH:17][C:12]=2[C:13]([O:15][CH3:16])=[O:14])=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27339602-Thiopheneboronic acidHCID 57667801HCID 57667801, compound

Product 1

HCID 57668051HCID 57668051, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

To a mixed solution of toluene 2.0 mL, ethanol 0.6 mL and water 0.4 mL of methyl 4-bromo-2-(4-fluoroanilino)benzoate 70 mg were added thiophene-2-boronic acid 42 mg, sodium carbonate 64 mg and tetrakis(triphenylphosphine)palladium(0) 13 mg at room temperature, and it was stirred under application of pressure at 160° C. for 5 minutes. After the reaction mixture was cooled to room temperature, insoluble matter was filtrated, and ethyl acetate and 0.5 mol/L hydrochloric acid were added to it. The organic layer was separated and collected,dried over anhydrous magnesium sulfate after sequential washing with 1.0 mol/L hydrochloric acid and saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Trikonex company, Flash Tube 2008, eluent; hexane] to give methyl 2-(4-fluoroanilino)-4-(thiophen-2-yl)benzoate. 2.0 mol/L Sodium hydroxide aqueous solution 1.0 mL was added to ethanol 7.0 mL solution of the obtained methyl 2-(4-fluoroanilino)-4-(thiophen-2-yl)benzoate, and it was stirred at room temperature for 1 hour and 30 minutes. 0.5 mol/L Hydrochloric acid and ethyl acetate were added to the reaction mixture, the organic layer was separated and collected, and the solvent was removed under reduced pressure. The obtained residue was refined by reversed-phase silica gel column chromatography [eluent; 50-100% acetonitrile/0.1% trifluoroacetic acid aqueous solution] to give 2-(4-fluoroanilino)-4-(thiophen-2-yl)benzoic acid 3.5 mg of pale yellow solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. filtrationinsoluble matter was filtrated
  3. additionethyl acetate and 0.5 mol/L hydrochloric acid were added to it
  4. customThe organic layer was separated
  5. washafter sequential washing with 1.0 mol/L hydrochloric acid and saturated sodium chloride aqueous solution
  6. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-8c4b715bc27f4147a4641e0cc1d2cb1b
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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