Lithium Hydroxide → 4-Ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid

HRID 1472604Notes

Reaction equation

HRID 1472604 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[C:6](=[O:17])[C:5]=1[C:18]([O:20]CC)=[O:19])[CH3:2].[Li+].[OH-]>CCO.O>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[C:6](=[O:17])[C:5]=1[C:18]([OH:20])=[O:19])[CH3:2]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 68735913Ethyl 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate

Product 1

HCID 585350974-Ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acidYield 79.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of ethyl 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate (60 g, 0.196 mol) and LiOH (30 g, 0.6 mol) in EtOH (200 mL) and water (100 mL) was stirred at RT for 16 h. The mixture was concentrated to remove EtOH, the aqueous residue diluted with additional water (300 mL), washed with EtOAc (1×) and acidified to pH<2 with conc. HCl. The mixture was extracted with EtOAc (3×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness. The residue was treated with pet ether and the resulting solid collected via filtration to afford 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (43 g, 79%). 1H NMR (400 MHz, DMSO-d6): δ 7.95 (d, J=8.0 Hz, 1H), 7.48 (m, 2H), 7.35 (m, 2H), 6.58 (d, J=7.6 Hz, 1H), 4.28 (q, J=7.2 Hz, 2H), 1.32 (t, J=7.2 Hz, 3H).

Workup

  1. concentrationThe mixture was concentrated
  2. customto remove EtOH
  3. additionthe aqueous residue diluted with additional water (300 mL)
  4. washwashed with EtOAc (1×)
  5. extractionThe mixture was extracted with EtOAc (3×)
  6. washthe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to dryness
  9. additionThe residue was treated with pet ether
  10. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-8068c20a1d3f4ec2ba72942ba9e4e4b6
Source dataset
uspto-grants-2015_04
Patent number
US09012635B2

Reaction notes

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