Potassium Phosphate, Tribasic → 5-Methyl-2-isopropyloxy-4-(pyridine-4-YL)-nitrobenzene

HRID 2046957Notes

Reaction equation

HRID 2046957 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](B(O)O)=[CH:3][CH:2]=1.Cl[C:11]1[CH:16]=[C:15]([O:17][CH:18]([CH3:20])[CH3:19])[C:14]([N+:21]([O-:23])=[O:22])=[CH:13][C:12]=1[CH3:24].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.N#N.C(OCC)(=O)C>[CH:18]([O:17][C:15]1[C:14]([N+:21]([O-:23])=[O:22])=[CH:13][C:12]([CH3:24])=[C:11]([C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)[CH:16]=1)([CH3:20])[CH3:19]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acidHCID 457903241-Chloro-5-isopropoxy-2-methyl-4-nitrobenzene

Product 1

HCID 597645455-Methyl-2-isopropyloxy-4-(pyridine-4-YL)-nitrobenzene

Reagents, catalysts & solvents 4

HCID 947NitrogenSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

4-Pyridineboronic acid (147 mg, 1.20 mmol, 1.1 equiv.) was dissolved in a 2:1 v/v mixture of dioxane and H2O (15 mL) and N2 was bubbled through for 5 minutes. Tris(dibenzylidene acetone)dipalladium (0) (100 mg, 0.109 mmol, 0.1 equiv.), 2-dicyclohexylphosphine-2′-6′-dimethoxy biphenyl (112 mg, 0.272 mmol, 0.25 equiv.), 1-chloro-5-isopropoxy-2-methyl-4-nitro-benzene (250 mg, 1.09 mmol, 1.0 equiv.) and K3PO4 (462 mg, 2.18 mmol, 2.0 equiv.) were added under a N2 blanket. The reaction vessel was sealed and heated with microwave irradiation to 150° C. for 20 minutes. After cooling to room temperature, the reaction was diluted with ethyl acetate and washed with 1N aqueous NaOH (twice). The organic layer was then dried over Na2SO4 and filtered. After concentration, the crude product was purified by silica gel chromatography (gradient from hexanes to 30% ethyl acetate in hexanes) to give 4-(5-Isopropoxy-2-methyl-4-nitro-phenyl)-pyridine as a brown solid: ESMS m/z 273.1 (M+H+).

Workup

  1. customwas bubbled through for 5 minutes
  2. customThe reaction vessel was sealed
  3. temperatureAfter cooling to room temperature
  4. washwashed with 1N aqueous NaOH (twice)
  5. dry with materialThe organic layer was then dried over Na2SO4
  6. filtrationfiltered
  7. concentrationAfter concentration
  8. customthe crude product was purified by silica gel chromatography (gradient from hexanes to 30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e6a44d7efc434e9d934c5c585666f2d3
Source dataset
uspto-grants-2013_11
Patent number
US08592432B2

Reaction notes

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