3-Aminopyridine → (3-Benzyloxy-5-bromo-phenyl)-pyridin-3-yl-amine

HRID 1784804Notes

Reaction equation

HRID 1784804 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:5]=[C:6]([Br:8])[CH:7]=1.[NH2:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1.CC(C)([O-])C.[Na+].CCOC(C)=O.CCCCCCC>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]>[CH2:10]([O:9][C:4]1[CH:3]=[C:2]([NH:17][C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[CH:7]=[C:6]([Br:8])[CH:5]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 100093-AminopyridineHCID 147841501-(Benzyloxy)-3,5-dibromobenzeneHCID 21899848Ethylacetate heptaneHCID 23676156Sodium t-butoxide

Product 1

HCID 50994027(3-Benzyloxy-5-bromo-phenyl)-pyridin-3-yl-amineYield 41%

Reagents, catalysts & solvents 3

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 57417360Sodium chloride; waterSolvent

Conditions

Temperature
85 °C

Procedure

An oven-dried flask was charged with (±)-BINAP (1.05 g, 1.68 mmol), Pd2(dba)3 CHCl3-complex (580 mg, 0.56 mmol) and then flushed with argon. Degassed toluene (28 mL) was added and the solution was stirred for 10 min. The catalyst solution was added to a mixture of 3,5-dibromo-1-benzyloxybenzene (38.3 g, 112 mmol), 3-aminopyridine (5.27 g, 56.0 mmol) and sodium tert-butoxide (7.54 g, 78.4 mmol) in degassed toluene (250 mL) and the mixture was heated to 80-90° C. for 24 h (conversion not complete). The reaction mixture was cooled to room temperature and brine (500 mL) was added. The mixture was extracted with ethyl acetate (500 mL) and the layers were separated. The organic layer was washed with brine (2×300 mL), dried (Na2SO4) and concentrated to give the crude product. FC (SiO2, AcOEt/heptane 2:1) gave 8.06 g (41%) of (3-benzyloxy-5-bromo-phenyl)-pyridin-3-yl-amine as yellow solid. 3,5-Dibromo-1-benzyloxybenzene was recovered, repurified and reused.

Workup

  1. customflushed with argon
  2. additionDegassed toluene (28 mL) was added
  3. temperatureThe reaction mixture was cooled to room temperature
  4. extractionThe mixture was extracted with ethyl acetate (500 mL)
  5. customthe layers were separated
  6. washThe organic layer was washed with brine (2×300 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customto give the crude product

Sources & evidence

ORD record
ord-eb7f12fb6a90449b92cf25742e870b2d
Source dataset
uspto-grants-2009_03
Patent number
US07504401B2

Reaction notes

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