Example 3.2 Preparation of 4,6-dichloro-5-methoxypyrimidine: 5-methoxypyrimidine-4,6-diol (96.0 g, 676 mmol) and triethylamine (95.0 mL, 680 mmol) were suspended in anhydrous toluene (1.2 L) and heated to 100-105°C. A solution of anhydrous toluene (200 mL) with trichlorophosphate (140 mL, 1.5 mol) was added slowly and dropwise over 30 min. The reaction mixture was refluxed for 1 hour and cooled to room temperature. The toluene layer was decanted and ice water was added to the residue. The heavier black oil layer was separated, dilution was continued with ice water, and the mixture was extracted with toluene (2 x 200 mL). The toluene extracts were combined and the aqueous layer discarded. The organic phase was washed sequentially with saturated sodium bicarbonate solution (2×300 mL), saturated saline (400 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to afford the title compound 4,6-dichloro-5-methoxypyrimidine (103.4 g, 86% yield) as a white solid.1H NMR (CDCl3) δ 4.00 (s, 3H), 8.55 (s, 1H).
