Hydrogen Bromide → 6-Bromo-8-methylimidazo(1,2-a)pyridine

HRID 269028

Reaction equation

HRID 269028 reaction equation
[NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([Br:9])=[CH:4][N:3]=1.[CH2:10](OC(OCC)CBr)[CH3:11].Br.C([O-])(O)=O.[Na+]>CCO.CCOC(C)=O>[Br:9][C:5]1[CH:6]=[C:7]([CH3:8])[C:2]2[N:3]([CH:10]=[CH:11][N:1]=2)[CH:4]=1

Participants

7

Reactant 4

HCID 260Hydrogen BromideHCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 1379342-Amino-5-bromo-3-methylpyridineHCID 516892Sodium Bicarbonate

Product 1

HCID 52606476-Bromo-8-methylimidazo(1,2-a)pyridineYield 72%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of commercially available 2-amino-5-bromo-3-picoline (21.48 g, 115 mmol) and bromoacetaldehyde diethyl acetal (90%, 39.6 mL, 230 mmol) in EtOH (110 mL) was added 48% aq. HBr (11 mL) and the mixture was refluxed for 11 h. Cooled to 23° C., diluted with EtOAc, poured into sat. NaHCO3-sol., separated phases, washed with the organic layer with brine, dried over Na2SO4. Removal of the solvent in vacuum (not over 40° C. bath temperature) left an orange liquid, which was directly coated on silica gel for chromatography. Silica gel column filtration with heptane/EtOAc 50:50→0:100 gave the title compound as a light brown solid (17.36 g, 72%).MS (ISP) 211.0 [(M+H)+], 231.1 [(M+2+H)+].

Workup

  1. temperaturethe mixture was refluxed for 11 h
  2. custom, separated phases
  3. washwashed with the organic layer with brine
  4. dry with materialdried over Na2SO4
  5. customRemoval of the solvent in vacuum (not over 40° C. bath temperature)
  6. waitleft an orange liquid, which
  7. filtrationSilica gel column filtration with heptane/EtOAc 50:50→0:100

Sources & evidence

ORD record
ord-2d29d2ad114842fead208702adf9cfd8
Source dataset
uspto-grants-2008_11
Patent number
US07446113B2

Linked notes

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