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

HRID 388559Notes

Reaction equation

HRID 388559 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-nitrobenzene2×

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.) is dissolved in a 2:1 v/v mixture of dioxane and H2O (15 mL) and N2 is 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 (Intermediate 4, 250 mg, 1.09 mmol, 1.0 equiv.) and K3PO4 (462 mg, 2.18 mmol, 2.0 equiv.) are added under a N2 blanket. The reaction vessel is sealed and heated with microwave irradiation to 150° C. for 20 min. After cooling to room temperature, the reaction is diluted with ethyl acetate and washed with 1 N aqueous NaOH (2×), the organic layer is then dried over Na2SO4 and filtered. After concentration, the crude product is 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+Ft).

Workup

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

Sources & evidence

ORD record
ord-cfa2b883194f460592999ee9b047f2d7
Source dataset
uspto-grants-2013_02
Patent number
US08377921B2

Reaction notes

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