Sodium Chloride → Methyl 2,6-dichloro-5-methoxypyrimidine-4-carboxylate

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Reaction Steps

A solution of 2,6-dichloro-5-methoxy-pyrimidine-4-carbaldehyde (see Examples 6 and 7 above for methods for preparing this compound) (50 g, 0.24 mol) in methanol (1 L) and water (60 mL) was prepared. To the solution, sodium bicarbonate (400 g) was added. A 2 M solution of bromine (192 g, 1.2 mol) in methanol/water (600 mL, 9:1) was added, dropwise, to the pyrimidine solution for 45 minutes at 0° C. while stirring the mixture. The stirring was continued at the same temperature for 1 h. Later, the mixture was stirred at room temperature for 4 h. While stirring, the reaction mixture was thereafter poured onto a mixture of crushed ice (2 L), sodium bisulfite (50 g), and sodium chloride (200 g). The product was extracted with ethyl acetate (1 L×2), and the combined organic layer was dried over sodium sulfate and filtered. Evaporation of the solvent under reduced pressure produced a thick material, which was then solidified on long standing. This produced the title compound (50.8 g, 87% yield); LC-MS 238 (m+1); HPLC (95% acetonitrile buffered with 0.1% v/v acetic acid.

Provenance & Evidence