Chloroacetaldehyde → Methyl 5-({[(methyloxy)methyl]oxy}methyl)imidazo[1,2-a]pyridine-8-carboxylate

HRID 406290Notes

Reaction equation

HRID 406290 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[C:4]([CH2:12][O:13][CH2:14][O:15][CH3:16])[N:3]=1.C(=O)(O)[O-].[Na+].Cl[CH2:23][CH:24]=O>CO.O.C(Cl)Cl>[CH3:16][O:15][CH2:14][O:13][CH2:12][C:4]1[N:3]2[CH:23]=[CH:24][N:1]=[C:2]2[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1

Participants

7

Reactant 3

HCID 33Chloroacetaldehyde2×HCID 516892Sodium BicarbonateHCID 86710854Methyl 2-amino-6-({[(methyloxy)methyl]oxy}methyl)-3-pyridinecarboxylate

Product 1

HCID 86710849Methyl 5-({[(methyloxy)methyl]oxy}methyl)imidazo[1,2-a]pyridine-8-carboxylateYield 70.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of methyl 2-amino-6-({[(methyloxy)methyl]oxy}methyl)-3-pyridinecarboxylate (496 mg, 2.192 mmol) and sodium bicarbonate (193 mg, 2.302 mmol) in a mixture of methanol (15 mL) and water (7.5 mL) was added chloroacetaldehyde (50% wt. solution in water, 0.311 mL, 2.412 mmol). The mixture was heated to reflux for 2 hours when LCMS indicated that no reaction has occurred. More chloroacetaldehyde (0.311 mL, 2.412 mmol) was added and heating continued for 16 hours when LCMS indicated the reaction to be complete. The mixture was partitioned between ethyl acetate (50 mL) and saturated aqueous sodium bicarbonate (50 mL). The organic phase was separated and the aqueous phase back extracted with ethyl acetate (50 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo to give crude product (450 mg). This material was dissolved in DCM and purified on silica (50 g) using a 0-25% methanol-DCM gradient over 60 min. The appropriate fractions were combined and evaporated in vacuo to give the title compound as an orange oil (386 mg).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 hours when LCMS
  3. temperatureheating
  4. customthe reaction
  5. customThe mixture was partitioned between ethyl acetate (50 mL) and saturated aqueous sodium bicarbonate (50 mL)
  6. customThe organic phase was separated
  7. extractionthe aqueous phase back extracted with ethyl acetate (50 mL)
  8. dry with materialThe combined organic extracts were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give crude product (450 mg)
  12. custompurified on silica (50 g)
  13. customover 60 min
  14. customevaporated in vacuo

Sources & evidence

ORD record
ord-288bcba96702429ca02fe71727b21780
Source dataset
uspto-grants-2014_06
Patent number
US08754101B2

Reaction notes

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