4-Bromo-3-(trifluoromethyl)aniline → HCID 16050434, compound

HRID 1591828Notes

Reaction equation

HRID 1591828 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[CH3:13][N:14]1[C:18]([C:19]#[N:20])=[CH:17][CH:16]=[C:15]1B(O)O.[F-].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:6][C:5]1[CH:7]=[CH:8][C:2]([C:15]2[N:14]([CH3:13])[C:18]([C:19]#[N:20])=[CH:17][CH:16]=2)=[C:3]([C:9]([F:12])([F:11])[F:10])[CH:4]=1

Participants

5

Reactant 3

HCID 678524-Bromo-3-(trifluoromethyl)anilineHCID 522689Potassium FluorideHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acid

Product 1

HCID 16050434HCID 16050434, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
25 °C

Procedure

4-Bromo-3-trifluoromethylaniline (1.77 g, 7.4 mmol), 1-methyl-5-cyano-2-pyrrole-boronic acid (2.0 g, 13.3 mmol), KF (1.42 g, 24.4 mmol), and Pd2(dba)3 (179 mg, 0.185 mmol) were added to a 50 mL round bottom flask under nitrogen. The flask was sealed and purged with nitrogen for 5 minutes. THF (18.5 mL) was added and the mixture was purged with nitrogen for an additional 5 minutes. A solution of tri-t-butylphosphine (10% wt in hexanes) (1.1 mL, 0.37 mmol) was added via syringe and the mixture was stirred vigorously at 25° C. for 16 hours. The mixture was diluted with 250 mL of EtOAc, filtered through a plug of silica gel, washed through with 200 mL of EtOAc and concentrated to give a crude brown/black semi-solid. Purification via Isco chromatography (the Redisep® column, silica, gradient 5-100% ethyl acetate in hexane) afforded 5-[4-amino-2-(trifluoromethyl)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile as a white solid (1.8 g, 92%).

Workup

  1. customThe flask was sealed
  2. custompurged with nitrogen for 5 minutes
  3. additionTHF (18.5 mL) was added
  4. customthe mixture was purged with nitrogen for an additional 5 minutes
  5. additionA solution of tri-t-butylphosphine (10% wt in hexanes) (1.1 mL, 0.37 mmol) was added via syringe
  6. additionThe mixture was diluted with 250 mL of EtOAc
  7. filtrationfiltered through a plug of silica gel
  8. washwashed through with 200 mL of EtOAc
  9. concentrationconcentrated
  10. customto give a crude brown/black semi-solid
  11. customPurification via Isco chromatography (the Redisep® column, silica, gradient 5-100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-c29ddd90ccc948648911639d3331c19d
Source dataset
uspto-grants-2007_11
Patent number
US07291643B2

Reaction notes

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