General procedure for the synthesis of 2,6-dichloropyrimidine-4-carbonyl chloride from orotate monohydrate:
1. In a dry reaction flask, whey acid monohydrate (34.828 g, 200.0 mmol), phosphorus trichloride (100 mL, 1092 mmol) and N,N-dimethylformamide (20 drops) were added.
2. The reaction mixture was heated to 110 °C and the reaction was stirred at this temperature overnight.
3. After completion of the reaction, the mixture was cooled to room temperature.
4. Hexane (500 mL) was added to the cooled dark reaction mixture with vigorous stirring.
5. Separate the hexane layer and wash rapidly with deionized water (100 mL x 1) and saturated saline (100 mL x 1) in that order.
6. Dry the organic phase with anhydrous magnesium sulfate and filter to remove the desiccant.
7. The solvent was carefully evaporated under reduced pressure to afford 2,6-dichloropyrimidine-4-carbonyl chloride as a light yellow liquid (26.13 g, 123.6 mmol, 62% yield).
Product characterization: 1H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H).
