Oxalic Acid → (S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one

HRID 1691799Notes

Reaction equation

HRID 1691799 reaction equation
CC1CC(OC([N:11]2[CH:16]=[C:15]([Si](C(C)C)(C(C)C)C(C)C)[C:14](=[O:27])[CH2:13][CH:12]2[C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)=O)C(C(C)(C2C=CC=CC=2)C)CC1.C[O-].[Na+].C(O)(=O)C(O)=O>CO>[F:34][C:31]1[CH:32]=[CH:33][C:28]([C@@H:12]2[CH2:13][C:14](=[O:27])[CH:15]=[CH:16][NH:11]2)=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 971Oxalic AcidHCID 10942334Sodium MethoxideHCID 669062662-(4-fluoro-phenyl)-4-oxo-5-triisopropylsilanyl-3,4-dihydro-2H-pyridine-1-carboxylic acid 5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester

Product 1

HCID 59377679(S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-oneYield 36.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of 2-(4-fluoro-phenyl)-4-oxo-5-triisopropylsilanyl-3,4-dihydro-2H-pyridine-1-carboxylic acid 5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester (7.78 g, 12.8 mmol) in methanol (95 mL) was added 25% sodium methoxide in methanol (29.4 mL, 128.4 mmol). The mixture was heated at reflux for 16 h. After cooling to rt, oxalic acid (46.3 g, 512 mmol) was added and the mixture was stirred for 2 h. The solvent was evaporated to dryness. The crude was partitioned between ethyl acetate and water. The organic layer was washed with water, brine dried over MgSO4, filtered and concentrated to dryness. Purification by flash chromatography (hex:EtOAc/2:8-0:1) gave (S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one (0.886 g, 36%, ee 99.3%) as a yellow solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 16 h
  3. customThe solvent was evaporated to dryness
  4. customThe crude was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customPurification by flash chromatography (hex:EtOAc/2:8-0:1)

Sources & evidence

ORD record
ord-812e4b6dc3ad481fb0ad5fd1c078478b
Source dataset
uspto-grants-2012_04
Patent number
US08153809B2

Reaction notes

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