Chloroacetaldehyde → 7-Methylimidazo(1,2-a)pyridine

HRID 985501Notes

Reaction equation

HRID 985501 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.C(=O)([O-])O.[Na+].Cl[CH2:15][CH:16]=O>C(O)C.O>[NH3:1].[CH3:8][C:6]1[CH:5]=[CH:4][N:3]2[CH:15]=[CH:16][N:1]=[C:2]2[CH:7]=1

Participants

7

Reactant 3

HCID 33ChloroacetaldehydeHCID 15332-Amino-4-methylpyridineHCID 516892Sodium Bicarbonate

Product 2

HCID 222AmmoniaHCID 1366817-Methylimidazo(1,2-a)pyridineYield 100%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of 2-amino-4-methylpyridine (21.6 g, 0.2 mol) in ethanol (300 ml) was treated with sodium hydrogencarbonate (33.6 g, 0.4 mol) then with chloroacetaldehyde (42.4 ml of a 45 wt % solution in water, 0.3 mol) and this mixture was heated at reflux for 16 hours. The reaction was cooled then pre-adsorbed directly on to silica (200 g). Purification by dry flash chromatography, eluting with dichloromethane/methanol/conc. ammonia (95:4.5:0.5) gave 7-methylimidazo[1,2-α]pyridine as an oil (26.4 g, 100%) which crystallised on standing. 1H NMR (400 MHz, CDCl3) δH 2.39 (3H, s), 6.62 (1H, d, J 7), 7.37 (1H, s), 7.49 (1H, s), 7.55 (1H, s), 8.00 (1H, d, J 7); m/z (ES+) 132 (M++H).

Workup

  1. temperatureat reflux for 16 hours
  2. temperatureThe reaction was cooled
  3. customPurification
  4. customby dry flash chromatography
  5. washeluting with dichloromethane/methanol/conc

Sources & evidence

ORD record
ord-d0d1d10162d14e929e322f700470aa2d
Source dataset
uspto-grants-2005_03
Patent number
US06872731B2

Reaction notes

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