Ethyl Acetate → [3-Bromo-5-(4-methoxy-benzyloxy)-phenyl]-pyridin-3-yl-amine

HRID 1784805Notes

Reaction equation

HRID 1784805 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH:5]=[C:6]([Br:8])[CH:7]=1.[NH2:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1.C([O-])(C)(C)C.[Na+].CCOC(C)=O>C1(C)C=CC=CC=1.[Cl-].[Na+].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.C(Cl)(Cl)Cl.[Pd].[Pd].CCOC(C)=O.CCCCCCC>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][O:9][C:4]2[CH:3]=[C:2]([NH:19][C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[CH:7]=[C:6]([Br:8])[CH:5]=2)=[CH:12][CH:13]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 100093-AminopyridineHCID 23676156Sodium t-butoxideHCID 252583101,3-Dibromo-5-[(4-methoxyphenyl)methoxy]benzene

Product 1

HCID 50994028[3-Bromo-5-(4-methoxy-benzyloxy)-phenyl]-pyridin-3-yl-amine

Reagents, catalysts & solvents 4

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 1140TolueneSolventHCID 21899848Ethylacetate heptaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

An oven-dried flask was charged with (±)-BINAP (504 mg, 0.81 mmol), Pd2(dba)3 CHCl3-complex (278 mg, 0.27 mmol) and then flushed with argon. Degassed toluene (50 mL) was added and the solution was stirred for 10 min. A second oven-dried flask was charged with 3,5-dibromo-1-p-methoxy-benzyloxybenzene (20.0 g, 53.8 mmol), 3-aminopyridine (2.72 g, 26.9 mmol) and sodium tert-butanolate (3.61 g, 37.6 mmol) in degassed toluene (100 mL) and the mixture was heated to 90° C. The catalyst solution was then added to the mixture and the reaction mixture was stirred at 90° C. for 40 h. The reaction mixture was cooled to room temperature and brine (120 mL) and AcOEt (120 mL) were added and the mixture was filtered over Hyflo. The filtrate was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with AcOEt (2×100 mL) and the layers were separated. The organic layer was washed with brine (2×80 mL), dried (Na2SO4) and concentrated to give the crude product. FC (SiO2, AcOEt/heptane 1:2→2:1) gave 7.96 (75%) of (3-p-methoxybenzyloxy-5-bromo-phenyl)-pyridin-3-yl-amine as yellow oil. 3,5-Dibromo-1-p-methoxy-benzyloxybenzene was recovered, repurified and can be reused.

Workup

  1. customflushed with argon
  2. additionDegassed toluene (50 mL) was added
  3. additionThe catalyst solution was then added to the mixture
  4. stirringthe reaction mixture was stirred at 90° C. for 40 h
  5. temperatureThe reaction mixture was cooled to room temperature
  6. filtrationthe mixture was filtered over Hyflo
  7. customThe filtrate was transferred to a separatory funnel
  8. customthe layers were separated
  9. extractionThe aqueous layer was extracted with AcOEt (2×100 mL)
  10. customthe layers were separated
  11. washThe organic layer was washed with brine (2×80 mL)
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated
  14. customto give the crude product

Sources & evidence

ORD record
ord-9655981e253346789505a2b9054eb072
Source dataset
uspto-grants-2009_03
Patent number
US07504401B2

Reaction notes

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