Acetic Acid → 2-(6-Methyl-2-(4-methylphenyl)imidazo(1,2-a)pyridin-3-yl)acetic acid

HRID 1934882Notes

Reaction equation

HRID 1934882 reaction equation
[OH-].[K+].[CH3:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]=[C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][N:13]3[C:19]=2[C:20](=O)[C:21]([O:23]CC)=[O:22])=[CH:6][CH:5]=1.NN.C(O)(=O)C>O.C(O)C.CO>[CH3:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[N:11]=[C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][N:13]3[C:19]=2[CH2:20][C:21]([OH:23])=[O:22])=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 9321HydrazineHCID 14797Potassium Hydroxide2×HCID 111630496-Methyl-2-(4-methylphenyl)-alpha-oxo-imidazo[1,2-a]pyridine-3-acetic Acid Ethyl Ester

Product 1

HCID 114259872-(6-Methyl-2-(4-methylphenyl)imidazo(1,2-a)pyridin-3-yl)acetic acidYield 96.5%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A solution of potassium hydroxide (90% titre; 30.3 g; 0.48 mols) in water (225 mL) and ethanol (65 mL) is added with ethyl 2-(4-methylphenyl)-6-methylimidazo[1,2-a]-pyridine-3-glyoxalate (141.5 g; 0.44 mols). The suspension is refluxed to obtain a yellow-orange solution, which is concentrated to reach a temperature of 98-100° C. and added with hydrazine (51.7% titre, 27.5 g; 0.44 mols). The solution is refluxed for 14 hours, then cooled to about 60° C., added with potassium hydroxide (90% titre, 54.9 g; 0.88 mols), then distilled under atmospheric pressure to reach the inner temperature of 122÷124° C., keeping the resulting suspension under reflux until nitrogen evolution ceases. The mixture is cooled to about 100° C., diluted with water (500 mL), cooled at room temperature and filtered through Celite. The resulting clear solution is dropped in about one hour into an acetic acid solution (91 g; 1.52 mols) in methanol (500 mL). The resulting suspension is cooled to 0÷5° C., filtered and the solid is washed with water, then dried at 60° C. under vacuum to obtain 2-(4-methylphenyl)-6-methylimidazo[1,2-a]-pyridine-3-acetic acid (118.4 g, 98.5% titre, K.F. 1.4%, yield 96.5%).

Workup

  1. temperatureThe suspension is refluxed
  2. customto obtain a yellow-orange solution, which
  3. concentrationis concentrated
  4. customa temperature of 98-100° C.
  5. temperatureThe solution is refluxed for 14 hours
  6. distillationdistilled under atmospheric pressure
  7. customthe inner temperature of 122÷124° C.
  8. temperatureunder reflux until nitrogen evolution ceases
  9. temperatureThe mixture is cooled to about 100° C.
  10. additiondiluted with water (500 mL)
  11. temperaturecooled at room temperature
  12. filtrationfiltered through Celite
  13. temperatureThe resulting suspension is cooled to 0÷5° C.
  14. filtrationfiltered
  15. washthe solid is washed with water
  16. customdried at 60° C. under vacuum

Sources & evidence

ORD record
ord-ffb6356323de4e9dbd618ac73f55365a
Source dataset
uspto-grants-2002_05
Patent number
US06384226B2

Reaction notes

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