p-Toluenesulfonic acid → 5-Chloroimidazo[1,2-A]pyridine

HRID 2361647Notes

Reaction equation

HRID 2361647 reaction equation
CC1C=CC(S(O)(=O)=O)=CC=1.CO[CH:14](OC)[CH2:15][Cl:16].C([O-])(O)=O.[Na+].[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27](Cl)[N:26]=1>O.C(O)C>[Cl:16][C:15]1[N:26]2[CH:27]=[CH:28][N:24]=[C:25]2[CH:30]=[CH:29][CH:14]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 609862-Chloro-1,1-dimethoxyethaneHCID 2062462-Amino-6-chloropyridineHCID 516892Sodium Bicarbonate

Product 1

HCID 109537225-Chloroimidazo[1,2-A]pyridineYield 36%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent2×

Conditions

Temperature
65 °C

Procedure

To a solution of pTSA (103 mg, 0.65 mmol) in water (5 ml) and ethanol (20 ml) was added chloroacetaldehyde dimethyl acetal (2.0 g, 16.0 mmol) at room temperature. The reaction was stirred at 65° C. for 30 minutes and then cooled to room temperature and a saturated solution of NaHCO3 was added dropwise until pH 7 was reached. 2-Amino-6-chloropyridine (2.1 g, 16 mmol) in 4:1 ethanol:water (20 ml) was then added and the reaction was heated at reflux for 3 hours. After cooling and concentrating at reduced pressure, the residue was purified by FCC (98:2 DCM/MeOH) to give the title compound (850 mg, 36%) as brown oil.

Workup

  1. temperaturecooled to room temperature
  2. temperaturethe reaction was heated
  3. temperatureat reflux for 3 hours
  4. temperatureAfter cooling
  5. concentrationconcentrating at reduced pressure
  6. customthe residue was purified by FCC (98:2 DCM/MeOH)

Sources & evidence

ORD record
ord-c69ad1add1b240cfb95bdba03bc89e7e
Source dataset
uspto-grants-2014_04
Patent number
US08691804B2

Reaction notes

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