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

HRID 536342Notes

Reaction equation

HRID 536342 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH:9]([CH3:11])[CH3:10])[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][C:3]=1[CH3:15].[N:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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].O.O1CCOCC1>[CH:9]([O:8][C:6]1[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][C:3]([CH3:15])=[C:2]([C:19]2[CH:20]=[CH:21][N:16]=[CH:17][CH:18]=2)[CH:7]=1)([CH3:11])[CH3:10]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 671555871-Bromo-5-isopropoxy-2-methyl-4-nitrobenzene

Product 1

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

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 1-bromo-5-isopropoxy-2-methyl-4-nitrobenzene (Step 2, Ig, 3.65 mmol), pyridine-4-boronic acid (490 mg, 4 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (300 mg, 0.73 mmol) and potassium phosphate (1.55 g, 7.3 mmol) in mixed solvent of dioxane (15 mL) and water (7.5 mL) was added tris(dibenzylidene-acetone)dipalladium (0) (334 mg, 0.36 mmol). This mixture was sealed and purged with nitrogen for 3 minutes and then heated at 120° C. for 5 hours. The mixture was cooled to room temperature, filtered, and the filtrate was concentrated. After concentration, the crude product was purified with silica gel flash column chromatography (60% ethyl acetate in hexanes) to afford 4-(5-isopropoxy-2-methyl-4-nitrophenyl)pyridine a as yellow solid: ESMS m/z 273.2 (M+H+).

Workup

  1. customThis mixture was sealed
  2. custompurged with nitrogen for 3 minutes
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. concentrationAfter concentration
  7. customthe crude product was purified with silica gel flash column chromatography (60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9d1554c4d7024ee2bc8e13a535a6b640
Source dataset
uspto-grants-2014_10
Patent number
US08859574B2

Reaction notes

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