Ethyl 4-bromobenzoate → Ethyl 4-(pyridin-4-yl)benzoate

HRID 1192415Notes

Reaction equation

HRID 1192415 reaction equation
[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][CH:6]=1)[CH3:2].[N:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1>O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8]([C:16]2[CH:17]=[CH:18][N:13]=[CH:14][CH:15]=2)=[CH:7][CH:6]=1)[CH3:2]

Participants

6

Reactant 2

HCID 22043Ethyl 4-bromobenzoateHCID 2734379(Pyridin-4-yl)boronic acid

Product 1

HCID 15294733Ethyl 4-(pyridin-4-yl)benzoateYield 35.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

The 4-bromo-benzoic acid ethyl ester (1.00 g, 4.37 mmol), pyridine-4-boronic acid (537 mg, 4.37 mmol), and tetrakis(triphenylphosphine)palladium(0) (757 mg, 0.655 mmol) were degassed under nitrogen. The solids were dissolved in 15 mL of 1,4-dioxane and 2.6 mL of 2M sodium carbonate solution. The mixture was heated to 80° C. overnight completion and allowed to cool to room temperature. The contents were partitioned between ethyl acetate and water, and the aqueous was extracted with ethyl acetate. The combined organic was washed with water, brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography (silica gel eluted with 1:1 hexanes:EtOAc, Rf=0.2) to afford the pure 4-pyridin-4-yl-benzoic acid ethyl ester as a pale yellow solid (350 mg, 35%). 1H NMR (CDCl3, 400 MHz) δ 8.71 (d, J=4.4 Hz, 2H), 8.16 (d, J=8.0 Hz, 2H), 7.71 (d, J=8.0 Hz, 2H), 7.53 (d, J=4.4 Hz, 2H), 4.42 (q, J=7.2 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H). LCMS (APCI+) m/z 228 [M+H]+; Rt=2.81 min.

Workup

  1. temperatureto cool to room temperature
  2. customThe contents were partitioned between ethyl acetate and water
  3. extractionthe aqueous was extracted with ethyl acetate
  4. washThe combined organic was washed with water, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography (silica gel eluted with 1:1 hexanes:EtOAc, Rf=0.2)

Sources & evidence

ORD record
ord-5aac89be028548d69a2956408a3a94cd
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

Loading…