Reaction #685008

Reaction equation

hydrochloric acid

2-(6-methoxy-1-benzofuran-5-yl)-1-ethanol

tert-butanol

potassium tert-butoxide

→

yellow crystal

2-(2-(6-methoxy-1-benzofuran-5-yl)ethoxy)acetic acid

Solvents

N,N-dimethylformamide

ethyl acetate

water

Conditions

Workup

1. 1
   Temperaturewhile cooling on ice
2. 2
   workup.WAITat a room temperature for 2 hours
3. 3
   Otheran organic layer was separated
4. 4
   WashThe organic layer was successively washed with water
5. 5
   Dryinga saturated saline solution, and then dried over anhydrous magnesium sulfate
6. 6
   workup.DISTILLATIONThe solvent was then distilled away under a reduced pressure
7. 7
   workup.DISSOLUTIONThe residue was dissolved in 10.5 ml of a 90% aqueous ethanol solution
8. 8
   workup.ADDITIONThereafter, 0.91 g of sodium hydroxide was added
9. 9
   Temperaturethe obtained mixture was then heated
10. 10
    Temperatureto reflux for 3 hours
11. 11
    TemperatureAfter cooling
12. 12
    workup.ADDITIONwater and ethyl acetate were added to the reaction mixture
13. 13
    workup.ADDITIONThe pH of the obtained mixture was adjusted to pH 1 by addition of 6 mol/l hydrochloric acid
14. 14
    Otheran organic layer was separated
15. 15
    WashThe organic layer was successively washed with water
16. 16
    Dryinga saturated saline solution, and then dried over anhydrous magnesium sulfate
17. 17
    workup.DISTILLATIONThe solvent was then distilled away under a reduced pressure
18. 18
    workup.ADDITIONThereafter, diisopropyl ether was added to the residue
19. 19
    Otherprecipitated crystals
20. 20
    Filtrationwere then collected by filtration
21. 21
    WashThe obtained crystals were washed with diisopropyl ether
22. 22
    Otherdried

Procedure

1.75 g of 2-(6-methoxy-1-benzofuran-5-yl)-1-ethanol was dissolved in a mixed solution consisting of 7.0 ml of tert-butanol and 1.75 ml of N,N-dimethylformamide. Thereafter, 2.2 g of 1-chloroacetylpiperidine and 1.54 g of potassium tert-butoxide were added to the obtained solution, while cooling on ice. The obtained mixture was stirred at the same temperature for 30 minutes and then at a room temperature for 2 hours. Thereafter, water and ethyl acetate were added to the reaction mixture. The pH of the obtained mixture was adjusted to pH 1 by addition of 6 mol/l hydrochloric acid, and an organic layer was separated. The organic layer was successively washed with water and a saturated saline solution, and then dried over anhydrous magnesium sulfate. The solvent was then distilled away under a reduced pressure. The residue was dissolved in 10.5 ml of a 90% aqueous ethanol solution. Thereafter, 0.91 g of sodium hydroxide was added thereto, and the obtained mixture was then heated to reflux for 3 hours. After cooling, water and ethyl acetate were added to the reaction mixture. The pH of the obtained mixture was adjusted to pH 1 by addition of 6 mol/l hydrochloric acid, and an organic layer was separated. The organic layer was successively washed with water and a saturated saline solution, and then dried over anhydrous magnesium sulfate. The solvent was then distilled away under a reduced pressure. Thereafter, diisopropyl ether was added to the residue, and precipitated crystals were then collected by filtration. The obtained crystals were washed with diisopropyl ether and then dried, so as to obtain 1.42 g of a yellow crystal, 2-(2-(6-methoxy-1-benzofuran-5-yl)ethoxy)acetic acid.

Source