Chloroacetaldehyde → 7-Methoxyimidazo[1,2-a]pyridine

HRID 985529Notes

Reaction equation

HRID 985529 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH2:9])[CH:4]=1.Cl[CH2:11][CH:12]=O.C(=O)([O-])O.[Na+]>O.C(O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]2[CH:11]=[CH:12][N:9]=[C:5]2[CH:4]=1

Participants

6

Reactant 3

HCID 33ChloroacetaldehydeHCID 516892Sodium BicarbonateHCID 108987152-Amino-4-Methoxypyridine

Product 1

HCID 450881887-Methoxyimidazo[1,2-a]pyridineYield 45%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A stirred suspension of 4-methoxypyridin-2-ylamine (4.50 g, 36.3 mmol), chloroacetaldehyde (8.54 g of a 50 wt % solution in water, 54.4 mmol) and sodium hydrogencarbonate (6.09 g, 72.6 mmol) in ethanol (70 ml) was heated under reflux for 4 h. The solvent was evaporated and the residue partitioned between ethyl acetate and water. The organic layer was washed with brine, dried and evaporated to give an orange oil. Purification by silica gel chromatography eluting with 2% methanol in dichloromethane gave 7-methoxyimidazo[1,2-α]pyridine (2.40 g, 45%) as a brown oil. 1H NMR (400 MHz, CDCl3) δH 3.85 (3H, s), 6.50 (1H, d, J 7), 6.88 (1H, s), 7.41 (1H, s), 7.48 (1H, s), 7.92 (1H, d, J 7).

Workup

  1. temperatureunder reflux for 4 h
  2. customThe solvent was evaporated
  3. customthe residue partitioned between ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. customdried
  6. customevaporated
  7. customto give an orange oil
  8. customPurification by silica gel chromatography
  9. washeluting with 2% methanol in dichloromethane

Sources & evidence

ORD record
ord-578b46eb311a4ced8145e0bfb7f8660c
Source dataset
uspto-grants-2005_03
Patent number
US06872731B2

Reaction notes

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