3-Chloro-4-fluoroaniline → 4-Fluoro-3-(thiophen-2-yl)aniline

HRID 2356695Notes

Reaction equation

HRID 2356695 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl[C:47]1[CH:48]=[C:49]([CH:51]=[CH:52][C:53]=1[F:54])[NH2:50]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O.C1(C)C=CC=CC=1>[F:54][C:53]1[CH:52]=[CH:51][C:49]([NH2:50])=[CH:48][C:47]=1[C:2]1[S:1][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 97083-Chloro-4-fluoroanilineHCID 62657Potassium Phosphate, TribasicHCID 27339602-Thiopheneboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 578293344-Fluoro-3-(thiophen-2-yl)aniline

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

768 mg of thiophene-2-boronic acid, 90 mg of palladium(II) acetate, 328 mg of 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl, 1.7 g of potassium phosphate and 562 mg of 3-chloro-4-fluoroaniline were added to 8 ml of dry toluene. The mixture was stirred at 80° C. overnight under an argon atmosphere. The cooled reaction mixture was admixed with water and ethyl acetate, and filtered, and the filtrate was extracted by shaking three times with a mixture of ethyl acetate and toluene. The combined organic phases were dried over magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The chromatographic purification of the residue was effected by method [RP1]. 4-Fluoro-3-thiophen-2-yl-phenylamine (267.4) was obtained. Molecular weight 193.03 (C10H8FNS); retention time Rt=1.18 min. [B]; MS (ESI): 235.08 (MH++CH3CN).

Workup

  1. customThe cooled reaction mixture
  2. filtrationfiltered
  3. extractionthe filtrate was extracted
  4. stirringby shaking three times
  5. additionwith a mixture of ethyl acetate and toluene
  6. dry with materialThe combined organic phases were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe chromatographic purification of the residue

Sources & evidence

ORD record
ord-3d97ffa75636440fa341f1acd0653de9
Source dataset
uspto-grants-2010_07
Patent number
US07759366B2

Reaction notes

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