Sodium Carbonate → 2,5-Dimethyl-4-(pyridin-3-yl)aniline

HRID 536348Notes

Reaction equation

HRID 536348 reaction equation
Br[C:2]1[C:8]([CH3:9])=[CH:7][C:5]([NH2:6])=[C:4]([CH3:10])[CH:3]=1.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13](B(O)O)[CH:12]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C([O-])([O-])=O.[Na+].[Na+]>CCCCO.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]>[CH3:10][C:4]1[CH:3]=[C:2]([C:13]2[CH:12]=[N:11][CH:16]=[CH:15][CH:14]=2)[C:8]([CH3:9])=[CH:7][C:5]=1[NH2:6]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 81671304-Bromo-2,5-dimethylanilineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 582571172,5-Dimethyl-4-(pyridin-3-yl)aniline

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 2631-ButanolSolvent

Procedure

A suspension of 4-bromo-2,5-dimethylaniline (4.00 g, 20 mmol), pyridin-3-ylboronic acid (2.70 g, 11 mmol), Pd2(dba)3 (0.55 g, 0.6 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.98 g, 1.2 mmol) and Na2CO3 (10.6 g, 100 mmol) in n-BuOH (50 mL) was degassed by a stream of argon gas for 15 min. The reaction flask was sealed and placed in a pre-heated oil bath (115° C.). After stirring overnight, the reaction was cooled and filtered. The filter cake was washed with DCM and the filtrate was concentrated in vacuo. The resulting residue was dissolved in EtOAc (150 mL). EtOAC was sequentially washed with water (20 mL), brine (20 mL), dried over Na2SO4 and evaporated. The crude product was purified by silica chromatography (0-50% EtOAC in hexanes gradient) to give 2,5-dimethyl-4-(pyridin-3-yl)aniline as a yellow solid; ESMS m/z 199.1 (M+H+).

Workup

  1. customwas degassed by a stream of argon gas for 15 min
  2. customThe reaction flask was sealed
  3. customplaced in a pre-heated oil bath
  4. custom(115° C.)
  5. temperaturethe reaction was cooled
  6. filtrationfiltered
  7. washThe filter cake was washed with DCM
  8. concentrationthe filtrate was concentrated in vacuo
  9. dissolutionThe resulting residue was dissolved in EtOAc (150 mL)
  10. washEtOAC was sequentially washed with water (20 mL), brine (20 mL)
  11. dry with materialdried over Na2SO4
  12. customevaporated
  13. customThe crude product was purified by silica chromatography (0-50% EtOAC in hexanes gradient)

Sources & evidence

ORD record
ord-e90390f522e44009a109bc17cbc662f6
Source dataset
uspto-grants-2014_10
Patent number
US08859574B2

Reaction notes

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