反応 #1095117

反応方程式

sodium hydride

di-tert-butyl malonate

hydrochloric acid

2-(2-benzo[b]thiophen-5-ylethoxy)-acetic acid

sodium

di-tert-butyl malonate

oxalyl chloride

→

1-(2-benzo[b]thiophen-5-ylethoxy)-acetone

溶媒

ethyl acetate

methylene chloride

ethyl acetate

Water

tetrahydrofuran

N,N-dimethylformamide

反応条件

後処理

1. 1
   workup.ADDITIONare added to the solution
2. 2
   その他obtained above, and the mixture
3. 3
   その他thus formed
4. 4
   workup.DISTILLATIONThe solvent is distilled off under reduced pressure
5. 5
   workup.DISSOLUTIONthe residue is dissolved in 5 mL of tetrahydrofuran
6. 6
   その他the solution thus obtained
7. 7
   温度cooled temperature
8. 8
   その他The mixture thus obtained
9. 9
   workup.STIRRINGwas stirred at the same temperature as above for 30 minutes
10. 10
    その他the organic layer is separated
11. 11
    洗浄The organic layer is washed with saturated aqueous solution of sodium chloride
12. 12
    乾燥dried over anhydrous magnesium sulfate
13. 13
    workup.DISTILLATIONthe solvent is distilled off under reduced pressure
14. 14
    温度The residue is heated
15. 15
    温度under reflux together with 20 mL of methylene chloride and 10 ml of trifluoroacetic acid
16. 16
    workup.DISTILLATIONthe solvent is distilled off under reduced pressure
17. 17
    温度the residue is heated
18. 18
    その他a de-carbonization reaction
19. 19
    その他the organic layer is separated
20. 20
    洗浄The organic layer is washed with saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride successively
21. 21
    乾燥dried over anhydrous magnesium sulfate
22. 22
    workup.DISTILLATIONthe solvent is distilled off under reduced pressure
23. 23
    その他the residue is purified by column chromatography (eluent: n-hexane:ethyl acetate=7:1 to 5:1)

実験手順

In 50 mL of methylene chloride is dissolved 5.00 g of 2-(2-benzo[b]thiophen-5-ylethoxy)-acetic acid. At an ice-cooled temperature, 2.2 mL of oxalyl chloride and 0.1 mL of N,N-dimethylformamide are added to the solution obtained above, and the mixture thus formed is stirred at ambient temperature for 30 minutes. The solvent is distilled off under reduced pressure, the residue is dissolved in 5 mL of tetrahydrofuran, and the solution thus obtained is dropwise added to a tetrahydrofuran solution of sodium salt of di-tert-butyl malonate, prepared from 1.01 g of sodium hydride and 5.70 mL of di-tert-butyl malonate, at an ice-cooled temperature. The mixture thus obtained was stirred at the same temperature as above for 30 minutes. The reaction mixture is introduced into a mixture of ice water and ethyl acetate, pH is adjusted to 1.0 with 2 mol/L hydrochloric acid, and the organic layer is separated. The organic layer is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue is heated under reflux together with 20 mL of methylene chloride and 10 ml of trifluoroacetic acid, the solvent is distilled off under reduced pressure, and the residue is heated to make progress a de-carbonization reaction. Water and ethyl acetate are added to the reaction mixture, and the organic layer is separated. The organic layer is washed with saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride successively and dried over anhydrous magnesium sulfate, the solvent is distilled off under reduced pressure, and the residue is purified by column chromatography (eluent: n-hexane:ethyl acetate=7:1 to 5:1) to obtain 3.67 g of 1-(2-benzo[b]thiophen-5-ylethoxy)-acetone.

出典