Bromine → Methyl 3-bromoimidazo[1,2-A]pyridine-7-carboxylate

HRID 985514Notes

Reaction equation

HRID 985514 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[CH:12][N:13]=[C:7]2[CH:6]=1)=[O:4].C([O-])(=O)C.[Na+].[Br:19]Br.S([O-])([O-])=O.[Na+].[Na+]>[Br-].[K+].CO>[NH3:8].[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[C:11]([Br:19])=[CH:12][N:13]=[C:7]2[CH:6]=1)=[O:4]

Participants

8

Reactant 4

HCID 24408BromineHCID 24437Sodium SulfiteHCID 517045Sodium AcetateHCID 15096964Methyl imidazo(1,2-a)pyridine-7-carboxylate

Product 2

HCID 222AmmoniaHCID 45790121Methyl 3-bromoimidazo[1,2-A]pyridine-7-carboxylateYield 164.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 253877Potassium BromideSolvent

Procedure

Imidazo[1,2-α]pyridine-7-carboxylic acid methyl ester (0.53 g, 3.0 mmol) and sodium acetate (0.30 g, 3.6 mmol) were dissolved in a saturated solution of potassium bromide in methanol (5 ml) and cooled to 0° C. before dropwise addition of bromine (0.50 g, 3.2 mmol) over 5 min. The mixture was allowed to stir for 15 minutes before adding saturated sodium sulphite solution (1 ml). The reaction was evaporated to dryness and the residue partitioned between ethyl acetate and 10% sodium sulphate solution. The organics were washed with water, brine, dried over sodium sulphate and concentrated to give a yellow oil. This oil was purified by flash column chromatography on silica eluting with dichloromethane/methanol/conc. ammonia (gradient 99:1:0.1 through to 96:4:0.4) to give 3-bromo-imidazo[1,2-α]pyridine-7-carboxylic acid methyl ester (0.63 g, 83%) as a white solid. 1H NMR (400 MHz, CDCl3) δH 3.98 (3H, s), 7.55 (1H, dd, J 2 and 7), 7.79 (1H, s), 8.16 (1H, dd, J 2 and 7), 8.36 (1H, d, J 2).

Workup

  1. customThe reaction was evaporated to dryness
  2. customthe residue partitioned between ethyl acetate and 10% sodium sulphate solution
  3. washThe organics were washed with water, brine
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated
  6. customto give a yellow oil
  7. customThis oil was purified by flash column chromatography on silica eluting with dichloromethane/methanol/conc

Sources & evidence

ORD record
ord-92ca9be5cdf148c795c69b4bdf17d75d
Source dataset
uspto-grants-2005_03
Patent number
US06872731B2

Reaction notes

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