4-Bromo-2,6-diisopropylaniline → Biphenyl, 3,5-diisopropyl-4-amino-

HRID 539446Notes

Reaction equation

HRID 539446 reaction equation
Br[C:2]1[CH:8]=[C:7]([CH:9]([CH3:11])[CH3:10])[C:5]([NH2:6])=[C:4]([CH:12]([CH3:14])[CH3:13])[CH:3]=1.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.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].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>[CH:12]([C:4]1[CH:3]=[C:2]([C:2]2[CH:8]=[CH:7][CH:5]=[CH:4][CH:3]=2)[CH:8]=[C:7]([CH:9]([CH3:11])[CH3:10])[C:5]=1[NH2:6])([CH3:14])[CH3:13]

Participants

6

Reactant 2

HCID 117801144-Bromo-2,6-diisopropylanilineHCID 22031701Potassium phosphate, tribasic, monohydrate

Product 1

HCID 3025997Biphenyl, 3,5-diisopropyl-4-amino-Yield 100.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 22272177Toluene waterSolvent

Procedure

Dry nitrogen gas was bubbled into a mixture of 4-bromo-2,6-diisopropylaniline (35.1 g, 137 mmol), potassium phosphate tribasic monohydrate (126 g, 548 mmol) and 2-dicyclo-hexylphosphino-2′,6′-dimethoxybiphenyl [S-Phos] (2.250 g, 5.48 mmol) in toluene:water (10:1, 1400 mL) at room temperature for a period of 40 minutes. Pd2(dba)3 (1.255 g, 1.370 mmol) was then added to the mixture above. The reaction was refluxed under a nitrogen atmosphere and monitored by GC-MS. The reaction was complete after overnight refluxing. The reaction mixture was cooled down and the organic layer was separated, washed with water (3×) and filtered through a bed of Celite®. Toluene was removed in vacuum to give a crude oil which was purified by silica gel column chromatography using hexane/AcOEt: 9/1 to 85/15 as eluants. Pure fractions were distilled to afford the title compound as an oil (17.43 g, 50% yield).

Workup

  1. temperatureThe reaction was refluxed under a nitrogen atmosphere
  2. temperaturerefluxing
  3. temperatureThe reaction mixture was cooled down
  4. customthe organic layer was separated
  5. washwashed with water (3×)
  6. filtrationfiltered through a bed of Celite®
  7. customToluene was removed in vacuum
  8. customto give a crude oil which
  9. customwas purified by silica gel column chromatography
  10. distillationPure fractions were distilled

Sources & evidence

ORD record
ord-882d68de098c408984802ee1ced2e134
Source dataset
uspto-grants-2014_10
Patent number
US08871361B2

Reaction notes

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