Ethyl 3-formylimidazo[1,2-a]pyridine-2-carboxylate → Ethyl 3-[(2,5-dimethoxyphenyl)hydroxymethyl]-imidazolo[1,2-a]pyridine-2-carboxylate

HRID 2229205Notes

Reaction equation

HRID 2229205 reaction equation
[CH:1]([C:3]1[N:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]2=[N:5][C:4]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:2].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1[Mg]Br>C1COCC1.C([O-])(O)=O.[Na+]>[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1[CH:1]([OH:2])[C:3]1[N:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]2=[N:5][C:4]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13]

Participants

5

Reactant 2

HCID 10704014Ethyl 3-formylimidazo[1,2-a]pyridine-2-carboxylateHCID 178492591HCID 178492591, compound

Product 1

HCID 18466904Ethyl 3-[(2,5-dimethoxyphenyl)hydroxymethyl]-imidazolo[1,2-a]pyridine-2-carboxylateYield 57%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 872 mg (4.0 mmol) of ethyl 3-formyl-imidazolo[1,2-a]pyridine-2-carboxylate in 40 mL THF is treated at −50° C. with 4 mL (4.0 mmol) 1M 2,5-dimethoxyphenylmagnesium bromide in THF. The temperature is allowed to reach −10° C. over 3 hr, diluted with 25 mL sat. NaHCO3 and extracted with 3×50 mL ethyl acetate. The combined organics are washed with 50 mL water and 50 mL brine. The resulting organic layer is dried over anhydrous MgSO4 and the solvent removed in vacuo. The residue is flash chromatographed with 1% methanol in dichloromethane to afford 800 mg (57%) ethyl 3-[(2,5-dimethoxyphenyl)hydroxymethyl]-imidazolo[1,2-a]pyridine-2-carboxylate.

Workup

  1. extractionextracted with 3×50 mL ethyl acetate
  2. washThe combined organics are washed with 50 mL water and 50 mL brine
  3. dry with materialThe resulting organic layer is dried over anhydrous MgSO4
  4. customthe solvent removed in vacuo
  5. customchromatographed with 1% methanol in dichloromethane

Sources & evidence

ORD record
ord-e572c8631e11486786ca70a1b58f44aa
Source dataset
uspto-grants-2002_07
Patent number
US06420365B1

Reaction notes

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