Hydrochloric Acid → 1-(2-Benzo[b]thiophen-5-ylethoxy)-acetone

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.

1. additionare added to the solution
2. customobtained above, and the mixture
3. customthus formed
4. distillationThe solvent is distilled off under reduced pressure
5. dissolutionthe residue is dissolved in 5 mL of tetrahydrofuran
6. customthe solution thus obtained
7. temperaturecooled temperature
8. customThe mixture thus obtained
9. stirringwas stirred at the same temperature as above for 30 minutes
10. customthe organic layer is separated
11. washThe organic layer is washed with saturated aqueous solution of sodium chloride
12. dry with materialdried over anhydrous magnesium sulfate
13. distillationthe solvent is distilled off under reduced pressure
14. temperatureThe residue is heated
15. temperatureunder reflux together with 20 mL of methylene chloride and 10 ml of trifluoroacetic acid
16. distillationthe solvent is distilled off under reduced pressure
17. temperaturethe residue is heated
18. customa de-carbonization reaction
19. customthe organic layer is separated
20. washThe organic layer is washed with saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride successively
21. dry with materialdried over anhydrous magnesium sulfate
22. distillationthe solvent is distilled off under reduced pressure
23. customthe residue is purified by column chromatography (eluent: n-hexane:ethyl acetate=7:1 to 5:1)

ORD-Eintrag

ord-a1024ec5484a4d5dac9f16c057c58997

Quelldatensatz

uspto-grants-2004_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06797726B1