Bromine → 5-Bromo-6-methoxypyridine-3-carbaldehyde

HRID 1663006Notes

Reaction equation

HRID 1663006 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH:9]=[O:10])=[CH:5][CH:4]=1.C([O-])(=O)C.[Na+].[Br:16]Br>C(O)(=O)C>[Br:16][C:4]1[CH:5]=[C:6]([CH:9]=[O:10])[CH:7]=[N:8][C:3]=1[O:2][CH3:1]

Participants

5

Reactant 3

HCID 24408BromineHCID 517045Sodium AcetateHCID 33645766-Methoxypyridine-3-carbaldehyde

Product 1

HCID 123924165-Bromo-6-methoxypyridine-3-carbaldehyde

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Conditions

Temperature
90 °C

Procedure

(see Eur. J. Med. Chem.-Chim. Ther. 1977, 12, 531) 54.8 g (400 mMol) 6-methoxy-3-pyridinecarbaldehyde (Aldrich) are dissolved in 180 ml of acetic acid. 63.8 g (778 mMol) sodium acetate are added portionwise (slightly exothermic). Then a solution of 30 ml (582 mMol) of bromine in 120 ml of acetic acid is added dropwise during 30 min. The mixture is stirred for 5 h at 90° C., then cooled to RT and concentrated partially in vacuo. The residue is diluted with icewater, neutralized to pH 7.5 with 4 N NaOH and extracted with 4 portions of EtOAc. The organic layers are washed twice with water and brine, dried (Na2SO4) and concentrated in vacuo. Column chromatography (SiO2; CH2Cl2) of the resulting oil and crystallization from CH2Cl2/hexane gives the title compound: mp: 94-95° C.

Workup

  1. temperaturecooled to RT
  2. concentrationconcentrated partially in vacuo
  3. additionThe residue is diluted with icewater
  4. extractionextracted with 4 portions of EtOAc
  5. washThe organic layers are washed twice with water and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customColumn chromatography (SiO2; CH2Cl2) of the resulting oil and crystallization from CH2Cl2/hexane

Sources & evidence

ORD record
ord-1c5e955e5a424132b41fe0898358500d
Source dataset
uspto-grants-2011_10
Patent number
US08034814B2

Reaction notes

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