Hydrochloric Acid → 5-[Bis(methyloxy)methyl]-3-chloro-2-iodopyridine

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-chloro-6-iodo-3-pyridinecarbaldehyde (260 mg, 0.972 mmol), trimethyl orthoformate (1.064 ml, 9.72 mmol), HCl (3M in MeOH) (0.778 ml, 2.333 mmol), DCM (1.5 ml) and MeOH (1.5 ml) was stirred at 50° C. for 3 h. TLC showed full conversion. The solution was cooled to room temperature and concentrated under vacuum. The residue was diluted with sat. NaHCO3 and EtOAc. Extraction, drying (MgSO4), filtration, and concentration afforded 271.5 mg of crude material. Purification by flash chromatography using Flashmaster II, a 5 g silica gel cartridge, and mixtures of hexane and EtOAc as eluent afforded 5-[bis(methyloxy)methyl]-3-chloro-2-iodopyridine (239.9 mg, 79%) as a yellow oil. It will be used in the next step without further purification.

Provenance & Evidence