p-Toluenesulfonic acid → Ethyl 2-(imidazo[1,2-a]pyridin-3-yl)acetate

HRID 240245Notes

Reaction equation

HRID 240245 reaction equation
[CH2:1]([O:3][C:4](=[O:12])[CH:5]=[CH:6][CH:7](OC)OC)[CH3:2].C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1>C(#N)C.O.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:12])[CH2:5][C:6]1[N:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]2=[N:24][CH:7]=1)[CH3:2]

Participants

7

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 104392-AminopyridineHCID 68762381HCID 68762381, compound

Product 1

HCID 11171725Ethyl 2-(imidazo[1,2-a]pyridin-3-yl)acetateYield 73.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

Heat a mixture of 4,4-dimethoxy-but-2-enoic acid ethyl ester (43.5 g, 250 mmol) and p-toluenesulfonic acid (4.75 g, 25 mmol) in acetonitrile (240 mL) and water (15 mL) at reflux for 2 hours. Cool the reaction mixture to room temperature and add 2-aminopyridine (18.8 g, 200 mmol). Heat the mixture at reflux for 16 hours then cool to room temperature. Dilute the reaction mixture with ethyl acetate (1200 mL) and wash sequentially with saturated aqueous sodium bicarbonate (600 mL×3) and saturated aqueous sodium chloride (600 mL×2). Dry the organic phase over sodium sulfate and concentrate under reduced pressure to provide the desired compound as a brown oil (30 g, 73%).

Workup

  1. temperatureHeat
  2. temperatureat reflux for 2 hours
  3. temperatureHeat the mixture
  4. temperatureat reflux for 16 hours
  5. temperaturethen cool to room temperature
  6. washwash sequentially with saturated aqueous sodium bicarbonate (600 mL×3) and saturated aqueous sodium chloride (600 mL×2)
  7. dry with materialDry the organic phase over sodium sulfate
  8. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-413ae63b263f42aab24893c8613e8529
Source dataset
uspto-grants-2014_02
Patent number
US08648063B2

Reaction notes

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