Chloroacetaldehyde → Methyl 6-bromoimidazo[1,2-a]pyridine-7-carboxylate

HRID 420520Notes

Reaction equation

HRID 420520 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[C:9]([Br:10])=[CH:8][N:7]=[C:6]([NH2:11])[CH:5]=1.C([O-])(O)=O.[Na+].Cl[CH2:19][CH:20]=O>CCO>[CH3:1][O:2][C:3]([C:4]1[C:9]([Br:10])=[CH:8][N:7]2[CH:19]=[CH:20][N:11]=[C:6]2[CH:5]=1)=[O:12]

Participants

5

Reactant 3

HCID 33ChloroacetaldehydeHCID 516892Sodium BicarbonateHCID 25307230Methyl 2-amino-5-bromoisonicotinate

Product 1

HCID 57906576Methyl 6-bromoimidazo[1,2-a]pyridine-7-carboxylateYield 91.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-amino-5-bromo-isonicotinic acid methyl ester (500 mg, 2.16 mmol), NaHCO3 (309 mg, 3.68 mmol) and chloracetaldehyde (1.16 mL, 9.8 mmol) in EtOH (15 mL) was vigorously stirred and refluxed for 14 h. The reaction mixture was cooled to RT, concentrated under vacuum and the remaining residue was suspended in AcOEt (100 mL). The organic fraction was washed with water (2×50 mL), then dried over Na2SO4, filtered, and evaporated. The residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, [hexane/DCM 1:1]/TBME 95:5-100% TBME) to yield the title compound (505 mg, 1.98 mmol, 91%). MS: 255 [M+1]+; HPLC: AtRet=0.58 TLC: RF 0.16 (hexane/DCM/TBME 1:1:2).

Workup

  1. temperaturerefluxed for 14 h
  2. concentrationconcentrated under vacuum
  3. washThe organic fraction was washed with water (2×50 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, [hexane/DCM 1:1]/TBME 95:5-100% TBME)

Sources & evidence

ORD record
ord-094f558165b94efeadd276b2003c215a
Source dataset
uspto-grants-2012_01
Patent number
US08097617B2

Reaction notes

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