2-Fluoroaniline → 5-Bromo-3,4-difluoro-2-((2-fluorophenyl)amino)benzoic acid

HRID 1161790Notes

Reaction equation

HRID 1161790 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[Br:9][C:10]1[C:11]([F:21])=[C:12]([F:20])[C:13](F)=[C:14]([CH:18]=1)[C:15]([OH:17])=[O:16]>C1COCC1>[Br:9][C:10]1[C:11]([F:21])=[C:12]([F:20])[C:13]([NH:4][C:3]2[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=2[F:1])=[C:14]([CH:18]=1)[C:15]([OH:17])=[O:16]

Participants

4

Reactant 2

HCID 95842-FluoroanilineHCID 111186375-Bromo-2,3,4-trifluorobenzoic acid

Product 1

HCID 595193885-Bromo-3,4-difluoro-2-((2-fluorophenyl)amino)benzoic acidYield 57.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 2-fluoroaniline (4.27 ml, 44.3 mmol) in THF (30 ml) at −78° C. was added LIHMDS (66.6 ml, 1 M in THF, 66.6 mmol) dropwise. The reaction mixture was stirred for 10 min and a solution of 5-bromo-2,3,4-trifluorobenzoic acid (5.63 g, 22.2 mmol) in THF (40 ml) was added to the mixture. The reaction was slowly warmed to room temperature and stirred at this temperature for 4 h. The mixture was concentrated, quenched with 10% HCl solution (70 ml), and extracted with EtOAc (2×200 ml). The combined organic solution was dried over MgSO4 and concentrated to dryness. Purification by trituration with boiling CH2Cl2 gave 4.40 g (57%) of 5-bromo-3,4-difluoro-2-(2-fluorophenylamino)benzoic acid as a yellow solid.

Workup

  1. stirringstirred at this temperature for 4 h
  2. concentrationThe mixture was concentrated
  3. customquenched with 10% HCl solution (70 ml)
  4. extractionextracted with EtOAc (2×200 ml)
  5. dry with materialThe combined organic solution was dried over MgSO4
  6. concentrationconcentrated to dryness
  7. customPurification by trituration with boiling CH2Cl2

Sources & evidence

ORD record
ord-3a046960899b44c3b8753882f8c0da28
Source dataset
uspto-grants-2010_10
Patent number
US07820664B2

Reaction notes

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