3-Methoxy-4-trifluoromethylsulfonyloxybenzoic acid methyl ester → Methyl 3-methoxy-4-pyridin-2-ylbenzoate

HRID 7764Notes

Reaction equation

HRID 7764 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1OS(C(F)(F)F)(=O)=O)[C:6]([O:8][CH3:9])=[O:7].[Br-].[N:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[Zn+]>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.C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][N:22]=1)[C:6]([O:8][CH3:9])=[O:7]

Participants

5

Reactant 2

HCID 106151343-Methoxy-4-trifluoromethylsulfonyloxybenzoic acid methyl esterHCID 178418723HCID 178418723, compound

Product 1

HCID 21990944Methyl 3-methoxy-4-pyridin-2-ylbenzoate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To 300 mL of degassed THF was added methyl 3-methoxy-4-{[(trifluoromethyl)sulfonyl]oxy}benzoate (20.95 g, 66.7 mmol), 2-pyridylzinc bromide (200 mL of 0.5M solution in THF, 100 mmol), and tetrakis(triphenylphosphine)palladium(0) (5.00 g, 4.3 mmol). The mixture was degassed with argon for an additional 30 minutes and heated at reflux under an argon atmosphere overnight. The reaction mixture was cooled to rt and concentrated in vacuo. The resultant brown residue was partitioned between EtOAc (1500 mL) and 50% saturated NaHCO3 (1000 mL). The aqueous layer was extracted with EtOAc (500 mL), and the combined organic layers washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography (0–25% EtOAc/hexanes) to give methyl 3-methoxy-4-pyridin-2-ylbenzoate as a colorless solid. 1H NMR (DMSO-d6, 300 MHz) δ 8.70 (d, 1H), 7.92–7.83 (m, 3H), 7.70–7.65 (m, 2H), 7.40–7.36 (m, 1H), 3.91 (s, 3H), 3.90 (s, 3H).

Workup

  1. customThe mixture was degassed with argon for an additional 30 minutes
  2. temperatureheated
  3. temperatureat reflux under an argon atmosphere overnight
  4. concentrationconcentrated in vacuo
  5. customThe resultant brown residue was partitioned between EtOAc (1500 mL) and 50% saturated NaHCO3 (1000 mL)
  6. extractionThe aqueous layer was extracted with EtOAc (500 mL)
  7. washthe combined organic layers washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography (0–25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ba8606b425c74166b50320df786dbb82
Source dataset
uspto-grants-2006_08
Patent number
US07087601B2

Reaction notes

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