Trimethyl orthoformate → 2-Bromo-5-chloro-4-(dimethoxymethyl)pyridine

HRID 2428090Notes

Reaction equation

HRID 2428090 reaction equation
[Br:1][C:2]1[CH:7]=[C:6](C=O)[C:5]([Cl:10])=[CH:4][N:3]=1.[CH:11](OC)([O:14][CH3:15])[O:12][CH3:13]>CO.CC1C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[CH:7]=[C:6]([CH:11]([O:14][CH3:15])[O:12][CH3:13])[C:5]([Cl:10])=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 9005Trimethyl orthoformateHCID 454803452-Bromo-5-chloropyridine-4-carbaldehyde

Product 1

HCID 575173382-Bromo-5-chloro-4-(dimethoxymethyl)pyridineYield 97.5%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 887MethanolSolvent

Procedure

To a sol. of 2-bromo-5-chloro-pyridine-4-carbaldehyde (43.9 g, 199 mmol) in MeOH (800 mL) were successively added at rt trimethyl orthoformate (65.3 mL, 597 mmol) and p-TsOH (1.90 g, 10.0 mmol). This reaction mixture was then heated to reflux for 3 h. The mixture was allowed to cool to rt, and was concentrated under reduced pressure. The residue was dissolved in CH2Cl2, and the mixture was washed with aq. 10% K2CO3. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Drying the residue under high vacuum yielded the crude title compound (51.7 g, 97%) that was used further without purification. LC-MS: tR=0.92 min; ES+: 309.06.

Workup

  1. temperatureThis reaction mixture was then heated
  2. temperatureto reflux for 3 h
  3. concentrationwas concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in CH2Cl2
  5. washthe mixture was washed with aq. 10% K2CO3
  6. dry with materiallayer was dried over MgSO4
  7. filtrationfiltered
  8. customthe solvents were removed under reduced pressure
  9. customDrying the residue under high vacuum

Sources & evidence

ORD record
ord-63e5d36091ab469087710c4292fbae64
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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