Ethyl Acetate → 4-[3-(1-Methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-3-oxo-1-o-tolyl-propyl]-benzoic acid

HRID 1617704Notes

Reaction equation

HRID 1617704 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])[CH2:9][C:10]([C:12]2[CH:13]=[CH:14][C:15](=[O:19])[N:16]([CH3:18])[CH:17]=2)=[O:11])=[CH:4][CH:3]=1.[C:27]([O-])([OH:29])=[O:28].[Na+].C(OCC)(=O)C.[C]=O>[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.Cl[Pd]Cl.[Fe+2].O>[CH3:18][N:16]1[C:15](=[O:19])[CH:14]=[CH:13][C:12]([C:10](=[O:11])[CH2:9][CH:8]([C:5]2[CH:4]=[CH:3][C:2]([C:27]([OH:29])=[O:28])=[CH:7][CH:6]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])=[CH:17]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 666685075-[3-(4-Bromo-phenyl)-3-o-tolyl-propionyl]-1-methyl-1H-pyridin-2-oneHCID 178418416HCID 178418416, compound

Product 1

HCID 670155254-[3-(1-Methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-3-oxo-1-o-tolyl-propyl]-benzoic acidYield 94%

Reagents, catalysts & solvents 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Procedure

A mixture of 5-[3-(4-bromo-phenyl)-3-o-tolyl-propionyl]-1-methyl-1H-pyridin-2-one (150 mg, example 162, step 3), dichloro(1,1′-bis(diphenylphosphino)ferrocene)palladium(II) dichloromethane adduct (30 mg), NaHCO3 (77 mg), ethyl acetate (4.5 ml) and water (1.5 ml) was treated with carbon monoxide at 150° C./80 bar for 20 h. After cooling to room temperature, the mixture was filtered. The filter cake was washed with ethyl acetate and with aqueous KHSO4 solution. The combined filtrate was extracted with ethyl acetate. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to dryness. The residue was taken up in 1 M aqueous NaOH solution and washed with diethyl ether. The aqueous phase was acidified using concentrated aqueous HCl and extracted with ethyl acetate. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to dryness to give the title compound (129 mg) as a light brown solid, MS (ESI−): m/z=374.1 [M−H]−.

Workup

  1. filtrationthe mixture was filtered
  2. washThe filter cake was washed with ethyl acetate and with aqueous KHSO4 solution
  3. extractionThe combined filtrate was extracted with ethyl acetate
  4. washThe organic phase was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. washwashed with diethyl ether
  9. extractionextracted with ethyl acetate
  10. washThe organic phase was washed with brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-35f5c04069c74f5a8833a7bd9181200b
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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