3-methoxy-4-[(E)-3-oxo-3-(2-phenylamino-pyridin-3-yl)-propenyl]-benzoic acid methyl ester → 3-Methoxy-4-[3-oxo-3-(2-phenylamino-pyridin-3-yl)-propyl]-benzoic acid methyl ester

HRID 1261768Notes

Reaction equation

HRID 1261768 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7](/[CH:10]=[CH:11]/[C:12](=[O:26])[C:13]2[C:14]([NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:15][CH:16]=[CH:17][CH:18]=2)=[C:6]([O:27][CH3:28])[CH:5]=1.[H][H]>C(OCC)(=O)C.[Pd]>[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12](=[O:26])[C:13]2[C:14]([NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:15][CH:16]=[CH:17][CH:18]=2)=[C:6]([O:27][CH3:28])[CH:5]=1

Participants

5

Reactant 2

HCID 866720533-methoxy-4-[(E)-3-oxo-3-(2-phenylamino-pyridin-3-yl)-propenyl]-benzoic acid methyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 708170873-Methoxy-4-[3-oxo-3-(2-phenylamino-pyridin-3-yl)-propyl]-benzoic acid methyl esterYield 35.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-methoxy-4-[(E)-3-oxo-3-(2-phenylamino-pyridin-3-yl)-propenyl]-benzoic acid methyl ester (875 mg, 2.25 mmol) in ethyl acetate was treated with 10% palladium on activated carbon (83 mg). The reaction was stirred under a balloon of hydrogen gas for 6 h. At this time, the reaction was filtered through a pad of Celite®, rinsed with ethyl acetate and concentrated in vacuo. LCMS indicated incomplete conversion to the desired product. Due to solubility issues, the residue was dissolved in acetone (200 mL) at 25° C. and was treated with 10% palladium on activated carbon (83 mg). The reaction was stirred under a balloon of hydrogen gas for 2 d. At this time, the reaction was filtered through a pad of Celite®, rinsed extensively with acetone and concentrated in vacuo. LCMS still indicated incomplete conversion to the desired product. The residue was dissolved in methylene chloride (150 mL) at 25° C. and was treated with 10% palladium on activated carbon (83 mg). The reaction was stirred under a balloon of hydrogen gas for 4 d. At this time, the reaction was filtered through a pad of Celite®, rinsed with methylene chloride (2×50 mL) and concentrated in vacuo. Flash chromatography (40 g silica column, 10-25% ethyl acetate/hexanes) afforded 3-methoxy-4-[3-oxo-3-(2-phenylamino-pyridin-3-yl)-propyl]-benzoic acid methyl ester (313.4 mg, 35.6%) as a yellow solid.

Workup

  1. filtrationAt this time, the reaction was filtered through a pad of Celite®
  2. washrinsed with ethyl acetate
  3. concentrationconcentrated in vacuo
  4. dissolutionDue to solubility issues, the residue was dissolved in acetone (200 mL) at 25° C.
  5. additionwas treated with 10% palladium on activated carbon (83 mg)
  6. filtrationAt this time, the reaction was filtered through a pad of Celite®
  7. washrinsed extensively with acetone
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in methylene chloride (150 mL) at 25° C.
  10. additionwas treated with 10% palladium on activated carbon (83 mg)
  11. stirringThe reaction was stirred under a balloon of hydrogen gas for 4 d
  12. filtrationAt this time, the reaction was filtered through a pad of Celite®
  13. washrinsed with methylene chloride (2×50 mL)
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-78b08c524a04490eb4f4dfd5af9b88ae
Source dataset
uspto-grants-2013_06
Patent number
US08471027B2

Reaction notes

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