反応 #505934

反応方程式

ammonium chloride

ethylmagnesium chloride tetrahydrofuran

dimethyl acetylenedicarboxylate

methyl iodide

→

title compound

収率 14.0%

2-ethyl-3-methylmaleic acid dimethyl ester

収率 14.0%

溶媒

tetrahydrofuran

hexamethylphosphoric triamide

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   workup.STIRRINGThe mixture was stirred at the same temperature for 2 h
2. 2
   workup.STIRRINGfurther stirred at −78° C. for 5 min
3. 3
   workup.STIRRINGAfter stirring for 20 min
4. 4
   温度the reaction mixture was warmed up to room temperature
5. 5
   温度the temperature was again raised to room temperature
6. 6
   その他The reaction solvent was evaporated under reduced pressure, and diethyl ether and water
7. 7
   workup.ADDITIONwere added
8. 8
   その他to separate the phases
9. 9
   抽出The aqueous layer was extracted three times with diethyl ether
10. 10
    洗浄the combined organic layer was washed with an aqueous solution of saturated ammonium chloridewater, and brine
11. 11
    その他The residue obtained
12. 12
    濃縮by concentrating the organic layer under reduced pressure

実験手順

To a suspension of bromo(dimethylsulfide)copper (I) (1.08 g, 5.25 mmol) in anhdrous tetrahydrofuran (24 mL), a 1.06 M ethylmagnesium chloride-tetrahydrofuran solution (4.8 mL, 5.1 mmol) was added dropwise under vigorous stirring at −50° C. The mixture was stirred at the same temperature for 2 h, and further stirred at −78° C. for 5 min. Then, a solution of dimethyl acetylenedicarboxylate (563 mg, 3.96 mmol) in tetrahydrofuran (8 mL) was added dropwise to the mixture. After 40 min, a solution of 4 mL of hexamethylphosphoric triamide in tetrahydrofuran (4 mL) was added dropwise, and a solution of methyl iodide (1.44 g, 10.1 mmol) in tetrahydrofuran (8 mL) was further added dropwise. After stirring for 20 min, the reaction mixture was warmed up to room temperature. An aqueous solution of saturated ammonium chloride (10 mL, adjusted to pH 8 with aqueous ammonia) was added at −20° C., and the temperature was again raised to room temperature. The reaction solvent was evaporated under reduced pressure, and diethyl ether and water were added to separate the phases. The aqueous layer was extracted three times with diethyl ether, and the combined organic layer was washed with an aqueous solution of saturated ammonium chloridewater, and brine. The residue obtained by concentrating the organic layer under reduced pressure was subjected to silica gel column chromatography (hexane-ethyl acetate 9:1) to give 98.2 mg of the title compound as a syrup (yield: 14%).

出典