Sodium Hydroxide → 6-Methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acid

HRID 559786Notes

Reaction equation

HRID 559786 reaction equation
[O:1]=[C:2]([NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=1)[CH2:3][C:4]([O:6]CC)=[O:5].C[O-].[Na+].CO[CH:25]=[CH:26][C:27](=O)[CH3:28].[OH-].[Na+]>CCO.O>[CH3:25][C:26]1[N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:17])([F:18])[F:19])[CH:11]=2)[C:2](=[O:1])[C:3]([C:4]([OH:6])=[O:5])=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 942973-Buten-2-one, 4-methoxy-HCID 3651864Ethyl 3-oxo-3-{[3-(trifluoromethyl)phenyl]amino}propanoateHCID 10942334Sodium Methoxide

Product 1

HCID 117021046-Methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acidYield 58%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of ethyl 3-oxo-3-{[3-(trifluoromethyl)phenyl]amino}propanoate (19.2 g, 70 mmol) and sodium methoxide (7.6 g, 140 mmol) in EtOH (250 ml) was added 4-methoxybut-3-en-2-one (90%) (7.72 g, 77 mmol). After the addition, the reaction mixture was refluxed for 2 h and then cooled. Water (50 ml) and 2M NaOH were added and the mixture was stirred at room temperature overnight. The organic solvents were removed and the reaction mixture was extracted (washed) with EtOAc. The water phases were acidified with hydrochloric acid to pH 3-4, an orange coloured precipitate appeared and was filtered off, washed with water and dried. Recrystallisation twice from heptane/EtOAc (4:1) afforded the title compound (12 g, 58%) as a white powder.

Workup

  1. additionAfter the addition
  2. temperaturethe reaction mixture was refluxed for 2 h
  3. temperaturecooled
  4. customThe organic solvents were removed
  5. extractionthe reaction mixture was extracted
  6. wash(washed) with EtOAc
  7. filtrationwas filtered off
  8. washwashed with water
  9. customdried
  10. customRecrystallisation twice from heptane/EtOAc (4:1)

Sources & evidence

ORD record
ord-899ba6f3eaa54025a8ea1a5ae13828e9
Source dataset
uspto-grants-2011_11
Patent number
US08063073B2

Reaction notes

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