Dimethyl Sulfate → Methyl (2E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyprop-2-enoate

Participants

Reaction Steps

Under the dried nitrogen atmosphere, to a reaction flask were added 150 mL of dichloromethane and 11.4 g of titanium tetrachloride, and then 6.4 g of trimethyl orthoformate was further added under violent stirring. After being stirred at room temperature for 1 hr, the mixture was cooled to −5° C., followed by adding thereto 13.9 g of methyl 2-(2-(6-chloropyrimidin-4-oxy)phenyl)acetate. The resultant was stirred for 30 min, and then 12.1 g of triethylamine was added and the resultant was stirred for 1 hr. The resulting reaction mixture was washed with 40 mL of 10% hydrochloric acid, dried with anhydrous magnesium sulfate and evaporated under vacuum to obtain a brown viscous substance. The brown viscous substance was dissolved in 100 mL of hot toluene, cooled to room temperature and then treated with 0.9 g of benzyltriethylammonium chloride, 15 g of 20% sodium hydroxide aqueous solution and 12.6 g of dimethyl sulfate. After that, the mixture was stirred at room temperature for 5 hrs, followed by being heated to 50° C., and the reaction went on under stirring for another 1 hr. The resulting mixture was washed with 50 mL of water, evaporated under reduced pressure and purified with flash column chromatography to obtain 14.6 g pale yellow solid. The yield was 91%.

Provenance & Evidence