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

Participants

Reaction Steps

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.

Provenance & Evidence