Acetic Acid → Ethyl 3-(hydroxymethyl)imidazo[1,2-a]pyridine-2-carboxylate

HRID 2229203Notes

Reaction equation

HRID 2229203 reaction equation
[N:1]1[C:2]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:3][N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.[C:15](O)(=[O:17])C.C([O-])(=O)C.[Na+].C=O>O>[OH:17][CH2:15][C:3]1[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]2=[N:1][C:2]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 517045Sodium AcetateHCID 818807Ethyl imidazo[1,2-a]pyridine-2-carboxylate

Product 1

HCID 18466901Ethyl 3-(hydroxymethyl)imidazo[1,2-a]pyridine-2-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 570 mg (3.0 mmol) ethyl imidazolo[1,2-a]pyridine-2-carboxylate, glacial acetic acid (0.8 mL) and 1 g (12 mmol) sodium acetate is treated with 6 mL 37% formaldehyde in water. The mixture is heated in a sealed tube at 90° C. for 6 hr and the acetic acid removed in vacuo. The residue is made basic by addition of 2M sodium hydroxide and extracted into 3×10 mL dichloromethane containing 1% methanol. The organic extract is dried over anhydrous MgSO4 and the solvent removed in vacuo to give the crude residue. The residue is flash chromatographed with initially 10% methanol in dichloromethane to afford 325 mg (49%) ethyl 3-(hydroxymethyl)-imidazolo[1,2-a]pyridine-2-carboxylate.

Workup

  1. customthe acetic acid removed in vacuo
  2. additionThe residue is made basic by addition of 2M sodium hydroxide
  3. extractionextracted into 3×10 mL dichloromethane containing 1% methanol
  4. extractionThe organic extract
  5. dry with materialis dried over anhydrous MgSO4
  6. customthe solvent removed in vacuo
  7. customto give the crude residue
  8. customchromatographed with initially 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-2fd88cfd8c674afeb1281a78a71116ba
Source dataset
uspto-grants-2002_07
Patent number
US06420365B1

Reaction notes

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