反应详情

To a solution of diethyl malonate (12 mL, 81 mmol) in ethanol (40 mL) was added dropwise 21% sodium ethoxide ethanol solution (29 mL, 77 mmol) under nitrogen atmosphere under ice-cooling. The mixture was warmed to room temperature, stirred for 1 hour, and cooled again with ice. The crude product (73 mmol) of 1-(1-chloro-1-methyl-2-methylsulfanyl-ethyl)-4-fluorobenzene or 1-(2-chloro-1-methyl-1-methylsulfanyl-ethyl)-4-fluorobenzene obtained in Example 1-3 was added dropwise to the mixture while maintaining a temperature below 4° C. The obtained solution was stirred for 1 hour at room temperature and concentrated under reduced pressure. The residue was neutralized by adding a 2N aqueous hydrochloric acid solution and the aqueous layer was extracted with ethyl acetate (50 mL). The organic layer was dried over magnesium sulfate, filtrated and the solvent was evaporated. Then the obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=20:1 to 5:1) to give the title compound (24 g, yield 84%) as a pale-yellow oil.

1. temperaturecooling
2. temperaturecooled again with ice
3. temperaturewhile maintaining a temperature below 4° C
4. stirringThe obtained solution was stirred for 1 hour at room temperature
5. concentrationconcentrated under reduced pressure
6. additionby adding a 2N aqueous hydrochloric acid solution
7. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
8. dry with materialThe organic layer was dried over magnesium sulfate
9. filtrationfiltrated
10. customthe solvent was evaporated
11. customThen the obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=20:1 to 5:1)