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

HRID 1672603Notes

Reaction equation

HRID 1672603 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 RT 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 to 4, an orange coloured precipitate appeared and was filtered off, washed with water and dried. Recrystallisation twice from heptane/EtOAc (4:1) afforded 6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxylic acid (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-5d5cfc3b53b641349bfbd40535dc9e84
Source dataset
uspto-grants-2011_08
Patent number
US07998984B2

Reaction notes

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