Thionyl Chloride → 4,6-Dimethoxypyrimidine-2-carbonyl chloride

A mixture consisting of 1.1 g (6.0 mmol) of 4,6-dimethoxypyrimidine-2-carboxylic acid, obtained in accordance with a method descibed in the specification of WO 9318012 A1, 1.1 g (9.0 mmol) of thionyl chloride, one drop of N,N-dimethylformamide and 5 ml of toluene was stirred under heating and refluxing for 3 hours. After the reaction, excess thionyl chloride and the solvent were removed under reduced pressure to obtain crystal of 4,6-dimethoxypyrimidine-2-carbonylchloride. In a separate vessel, 0.30 g (2.0 mmol) of 6,6-difluoro-5-methyl-5-hexenole and 0.61 g (3.0 mmol) of 4,6-dimethoxypyrimidine-2-carbonylchloride were dissolved in 10 ml of tetrahydrofuran, followed by the drop-wise addition of 0.40 g (4.0 mmol) of triethylamine at room temperature, followed by stirring at the same temperature for 1 hour. The reaction liquid was then poured in water and extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentration under reduced pressure. The residue was purified with silica gel column chromatography (ethyl acetate:hexane=1:7) to obtain 0.20 g (yield: 21%) of 6,6-difluoro-5-methyl-5-hexenyl 4,6-dimethoxypyrimidine-2-carboxylate.