Toluene → 1-(4-Ethoxycarbonyl-phenyl)-2-oxo-1,2-dihydro-pyridine-4-carboxylic acid

HRID 71722Notes

Reaction equation

HRID 71722 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][NH:8][C:7](=[O:11])[CH:6]=1)=[O:4].[OH-:12].C([N+](CC[CH2:28][CH3:29])(CCCC)CCCC)CCC.[OH-:30].[NH4+].[C:32]1([CH3:38])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>O>[CH2:28]([O:12][C:38]([C:32]1[CH:37]=[CH:36][C:35]([N:8]2[CH:9]=[CH:10][C:5]([C:3]([OH:2])=[O:4])=[CH:6][C:7]2=[O:11])=[CH:34][CH:33]=1)=[O:30])[CH3:29]

Participants

6

Reactant 4

HCID 1140TolueneHCID 14923Ammonium HydroxideHCID 280755Methyl 2-oxo-1,2-dihydropyridine-4-carboxylateHCID 2723671Tetrabutylammonium Hydroxide

Product 1

HCID 596114481-(4-Ethoxycarbonyl-phenyl)-2-oxo-1,2-dihydro-pyridine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 2-oxo-1,2-dihydro-pyridine-4-carboxylic acid methyl ester (2.00 g), 1.0M tetrabutylammonium hydroxide in H2O (13 ml) and toluene (50 mL) was stirred for 2 hours at ambient temperature. Mixture was concentrated and co-evaporated with toluene (3×100 mL) and dried under high vacuum. To the residue was added 4-Iodo-benzoic acid ethyl ester (2.40 g) and co-evaporated with toluene (2×20 mL). Copper iodide (0.829 g) and DMF (10 mL) were added and reaction mixture heated at 95° C. for 18 hours, protected from light. To the cooled reaction mixture was added 3N ammonium hydroxide and extracted with dichloromethane (4×). Organic layer was dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 0 to 5% methanol/dichloromethane+1% triethylamine) to give 1-(4-Ethoxycarbonyl-phenyl)-2-oxo-1,2-dihydro-pyridine-4-carboxylic acid (1.155 g) as the triethylammonium salt: LCMS-ESI−: calc'd for C15H12NO5: 286.27 (M−H+). Found: 286.1 (M−H+).

Workup

  1. concentrationMixture was concentrated
  2. customdried under high vacuum
  3. additionTo the residue was added 4-Iodo-benzoic acid ethyl ester (2.40 g)
  4. additionCopper iodide (0.829 g) and DMF (10 mL) were added
  5. customreaction mixture
  6. temperatureheated at 95° C. for 18 hours
  7. customTo the cooled reaction mixture
  8. extractionextracted with dichloromethane (4×)
  9. dry with materialOrganic layer was dried (MgSO4)
  10. concentrationconcentrated
  11. custompurified by flash column chromatography (silica gel, 0 to 5% methanol/dichloromethane+1% triethylamine)

Sources & evidence

ORD record
ord-fbb675d23dbb4a649ad6ac0866f1b76c
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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