4-chloro-2,5-diMethoxypyriMidine synthesis

Yield: 72%

Reaction Conditions:

with sodium hydroxide;triethylamine;trichlorophosphate in ice-water;toluene

Steps:

4 Example 4
Example 4 15.6 g (0.1 mol) of 2,5-dimethoxy-4-hydroxypyrimidine from Example 3 were suspended in 25 g of toluene. 46.0 g of phosphorus oxychloride were added and the suspension heated to 80° C. Within 1 hour, 20.2 g of triethylamine were added dropwise and the entire mixture was stirred at 80° C. for 30 minutes. The entire mixture was poured into 600 g of ice-water, stirred for 12 hours and adjusted to pH 5 using sodium hydroxide. The toluene phase was removed, and the aqueous phase extracted a further 3 times with 50 mol of toluene each time. The combined toluene extracts were concentrated to dryness. 12.57 g of 4-chloro-2,5-dimethoxypyrimidine were obtained in the form of slightly yellowish crystals of characteristic odor. Melting point: 78 to 80° C., ¹H-NMR: 3.860 ppm (s, 3H), 3.909 ppm (s, 3H), 8.446 ppm (s, 1H), ¹³C-NMR: 55.11 ppm (OCH₃), 57.42 ppm (OCH₃), 143.90 ppm (C₆), 145.09 ppm (C₅), 149.67 ppm (C₄), 158.28 ppm (C₂). GC/MS data: content>98%, M⁺ 174/176 g/mol. The yield was 72%.

References:

Güthner, Thomas;Neuhauser, Karl-Heinz US2003/22908, 2003, A1