Hydrochloric Acid → Ethyl 7-chloroimidazo[1,2-A]pyridine-3-carboxylate

HRID 706558Notes

Reaction equation

HRID 706558 reaction equation
Cl[C:2]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:3][O-].[K+].Cl.[Cl:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>CCO.O>[Cl:12][C:13]1[CH:18]=[CH:17][N:16]2[C:2]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:3][N:19]=[C:15]2[CH:14]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 10340Sodium CarbonateHCID 5818662-Amino-4-chloropyridineHCID 74089075Potassium 2-chloro-3-ethoxy-3-oxoprop-1-en-1-olate2×

Product 1

HCID 67107280Ethyl 7-chloroimidazo[1,2-A]pyridine-3-carboxylateYield 88.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A flask equipped with a reflux condenser, mechanical stirring, and an internal temperature probe, was charged with potassium 2-chloro-3-ethoxy-3-oxoprop-1-en-1-olate (58.70 g, 311.1 mmol) followed by addition 200 mL of EtOH to form a slurry. Aqueous hydrogen chloride (4.862 mL, 15.56 mmol) in EtOH was then added to the slurry. The slurry was stirred for about 15 minutes, and then 4-chloropyridin-2-amine (20.00 g, 155.6 mmol) was added, and the mixture was warmed to 70° C. After about one hour, an additional 2 equivalents of 3.2 M aqueous HCl were added and the mixture stirred at 70° C. for 16 hours. At this point, an additional 30 g of potassium 2-chloro-3-ethoxy-3-oxoprop-1-en-1-olate were added and the mixture stirred at 70° C. for 2 hours to facilitate completion of the reaction. The mixture was cooled to ambient temperature and 500 mL of water were added, followed by adjustment of the pH to 11 with 10% aqueous sodium carbonate. After stirring for several hours, the precipitated solids were collected by filtration and dried under vacuum to give 31 g (88%) of the desired compound.

Workup

  1. customA flask equipped with a reflux condenser
  2. customto form a slurry
  3. waitAfter about one hour
  4. stirringthe mixture stirred at 70° C. for 16 hours
  5. stirringthe mixture stirred at 70° C. for 2 hours
  6. customcompletion of the reaction
  7. temperatureThe mixture was cooled to ambient temperature
  8. stirringAfter stirring for several hours
  9. filtrationthe precipitated solids were collected by filtration
  10. customdried under vacuum

Sources & evidence

ORD record
ord-5ebfdb4a77444986bd5a376cf41849cd
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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