Ethylene Glycol → 2-Bromo-5-(1,3-dioxolan-2-YL)pyridine

HRID 78154Notes

Reaction equation

HRID 78154 reaction equation
[Br:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]=[O:9])=[CH:4][CH:3]=1.[CH2:10](O)[CH2:11][OH:12].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>O.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 117692346-Bromo-3-pyridinecarboxaldehyde

Product 1

HCID 184696682-Bromo-5-(1,3-dioxolan-2-YL)pyridineYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a toluene (100 mL) solution of 6-bromo-pyridine-3-carbaldehyde (5.0 g, 27 mmol) described in Manufacturing Example 154-1-1 were added ethylene glycol (3.0 mL, 54 mmol) and p-toluenesulfonic acid monohydrate (512 mg, 2.7 mmol), which was refluxed for 3 hours and 40 minutes under nitrogen atmosphere. Sodium hydrogencarbonate and water were added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (heptane: ethyl acetate=1:1) to obtain the title compound (6.0 g, 97%).

Workup

  1. temperaturewas refluxed for 3 hours and 40 minutes under nitrogen atmosphere
  2. extractionwas extracted with ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under a reduced pressure
  8. customthe residue was purified by NH silica gel column chromatography (heptane: ethyl acetate=1:1)

Sources & evidence

ORD record
ord-3b88243d65934b25afad8b552cc1064d
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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