Toluene → 3-{[4-(1-Methylethyl)phenoxy]methyl}pyridin-2-amine

HRID 1747909Notes

Reaction equation

HRID 1747909 reaction equation
CC(C)([O-])C.[Na+].C1(C(C2C=CC=CC=2)=[NH:14])C=CC=CC=1.Cl[C:22]1[C:27]([CH2:28][O:29][C:30]2[CH:35]=[CH:34][C:33]([CH:36]([CH3:38])[CH3:37])=[CH:32][CH:31]=2)=[CH:26][CH:25]=[CH:24][N:23]=1.C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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.C1COCC1>[CH3:37][CH:36]([C:33]1[CH:34]=[CH:35][C:30]([O:29][CH2:28][C:27]2[C:22]([NH2:14])=[N:23][CH:24]=[CH:25][CH:26]=2)=[CH:31][CH:32]=1)[CH3:38]

Participants

8

Reactant 4

HCID 1140TolueneHCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 624715482-Chloro-3-{[4-(1-methylethyl)phenoxy]methyl}pyridine

Product 1

HCID 150356783-{[4-(1-Methylethyl)phenoxy]methyl}pyridin-2-amineYield 87%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of sodium tert-butoxide (0.617 g), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.160 g), 1,1-diphenylmethanimine (1.008 g), 2-chloro-3-{[4-(1-methylethyl)phenoxy]methyl}pyridine (1.12 g), tris(dibenzylideneacetone)dipalladium(0) (0.118 g) and toluene (20 mL) was stirred at 110° C. for 6 hr. To the reaction mixture was added THF, and the mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. To the residue were added THF (25 mL) and 1M hydrochloric acid (25 mL) at room temperature, and the mixture was stirred overnight. The reaction mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate/hexane) to give the title compound (902.2 mg) containing impurity as a pale-yellow oil.

Workup

  1. filtrationthe mixture was filtered through celite
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. additionTo the residue were added THF (25 mL) and 1M hydrochloric acid (25 mL) at room temperature
  4. stirringthe mixture was stirred overnight
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with water and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by basic silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a259f5059e03448faf92b0063f321b90
Source dataset
uspto-grants-2015_10
Patent number
US09150591B2

Reaction notes

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