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

HRID 1050856Notes

Reaction equation

HRID 1050856 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 78.9%

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. The residue was diluted with water (300 mL) and was washed with EtOAc (100 mL). The aqueous layer was acidified to pH<2 with conc HCl and was extracted with EtOAc (3×300 mL). The extracts were washed with brine, dried over Na2SO4 and concentrated. Petroleum ether (PE) (200 mL) was added. The resultant precipitate was collected by filtration, washed with PE and dried to afford 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid. (43 g, 78.9% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.95 (d, J=8.0 Hz, 1 H), 7.48 (m, 2 H), 7.35 (m, 2 H), 6.58 (d, J=7.6 Hz, 1 H), 4.28 (q, J=7.2 Hz, 2 H), 1.32 (t, J=7.2 Hz, 3 H).

Workup

  1. concentrationThe mixture was concentrated
  2. additionThe residue was diluted with water (300 mL)
  3. washwas washed with EtOAc (100 mL)
  4. extractionwas extracted with EtOAc (3×300 mL)
  5. washThe extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. additionPetroleum ether (PE) (200 mL) was added
  9. filtrationThe resultant precipitate was collected by filtration
  10. washwashed with PE
  11. customdried

Sources & evidence

ORD record
ord-6e0bb7b0346643eb8e66fc1340e8c657
Source dataset
uspto-grants-2016_07
Patent number
US09387202B2

Reaction notes

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