1-Bromo-3,5-bis(trifluoromethyl)benzene → HCID 86655697, compound

HRID 2047482Notes

Reaction equation

HRID 2047482 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5](Br)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH:16]1([NH2:19])[CH2:18][CH2:17]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:16]1([NH:19][C:5]2[CH:4]=[C:3]([C:2]([F:15])([F:14])[F:1])[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=2)[CH2:18][CH2:17]1

Participants

8

Reactant 3

HCID 676021-Bromo-3,5-bis(trifluoromethyl)benzeneHCID 69828CyclopropylamineHCID 23676156Sodium t-butoxide

Product 1

HCID 86655697HCID 86655697, compoundYield 76.2%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of 3,5-bis(trifluoromethyl)bromobenzene (10 g), cyclopropylamine (2.4 g) and (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.3 g) in toluene (100 mL) was added palladium acetate (0.16 g) under a nitrogen atmosphere, and the mixture was stirred at room temperature for 20 min. To this mixture was added sodium tert-butoxide (4.7 g), and the mixture was stirred at 100° C. for 2 hr. The mixture was cooled, diluted with water, and extracted with ethyl acetate. The extract was washed with water and saturated brine, dried, filtered through silica gel (eluted with 20% ethyl acetate/hexane), and concentrated under reduced pressure. The residue was diluted with hexane, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (solvent gradient; 0→10% ethyl acetate/hexane) to give N-cyclopropyl-3,5-bis(trifluoromethyl)aniline (7.0 g, 74%) as an orange oil.

Workup

  1. stirringthe mixture was stirred at 100° C. for 2 hr
  2. temperatureThe mixture was cooled
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with water and saturated brine
  5. customdried
  6. filtrationfiltered through silica gel (eluted with 20% ethyl acetate/hexane)
  7. concentrationconcentrated under reduced pressure
  8. additionThe residue was diluted with hexane
  9. filtrationthe insoluble material was filtered off
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was separated
  12. custompurified by silica gel column chromatography (solvent gradient; 0→10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-031c71c448b64030889dc2dbf3a6b7c9
Source dataset
uspto-grants-2013_11
Patent number
US08592454B2

Reaction notes

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