Chloroacetaldehyde → Ethyl imidazo[1,2-a]pyridine-6-carboxylate

HRID 487267Notes

Reaction equation

HRID 487267 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1)=[O:5])[CH3:2].Cl[CH2:14][CH:15]=O>C1(C)C=CC=CC=1>[C:4]([C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:14]=[CH:15][N:12]=2)[CH:11]=1)([O:3][CH2:1][CH3:2])=[O:5]

Participants

4

Reactant 2

HCID 33ChloroacetaldehydeHCID 235927Ethyl 6-Aminonicotinate

Product 1

HCID 11830209Ethyl imidazo[1,2-a]pyridine-6-carboxylateYield 60.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2-amino-5-pyridine carboxylic acid ethyl ester (4.5 g, 27.1 mmol), chloroacetaldehyde (5.7 ml, 40.6 mmol, 45% w/w in water) and toluene (125 ml) was heated to reflux and water was collected in a Dean Stark trap. After 3 hours at reflux the reaction mixture was cooled to room temperature and the resulting precipitate was collected by filtration and washed with ether. The solid was dissolved in water and the solution was neutralized by the addition of concentrated aqueous ammonium hydroxide. The aqueous layer was extracted with chloroform, the organic layer was washed with brine and the solvent was removed in vacuo. The residue was dissolved in ethyl acetate, treated with charcoal and passed through a plug of silica. Removal of the solvent in vacuo afforded 3.1 g (60%) of 6-carboethoxy imidazo[1,2-a]-pyridine as an off-white solid, m.p. 93°-94° C. when recrystallized from tert-butylmethyl ether and dried for 16 hours at 50° C. in high vacuum.

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. customwater was collected in a Dean Stark trap
  4. temperatureAfter 3 hours at reflux the reaction mixture
  5. filtrationthe resulting precipitate was collected by filtration
  6. washwashed with ether
  7. dissolutionThe solid was dissolved in water
  8. additionthe solution was neutralized by the addition of concentrated aqueous ammonium hydroxide
  9. extractionThe aqueous layer was extracted with chloroform
  10. washthe organic layer was washed with brine
  11. customthe solvent was removed in vacuo
  12. dissolutionThe residue was dissolved in ethyl acetate
  13. additiontreated with charcoal
  14. customRemoval of the solvent in vacuo

Sources & evidence

ORD record
ord-1aacbb049ed142eda2d2794b1c8fac87
Source dataset
uspto-grants-1994_03
Patent number
US05294612

Reaction notes

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