Reaktion #684991

Reaktionsgleichung

3-(2-(1-benzothiophene-5-yl)ethoxy)-1-(3-hydroxy-1-azetidinyl)-1-propanone

sodium borohydride

hydrochloric acid

→

1-(3-(2-(1-benzothiophene-5-yl)ethoxy)propyl)-3-azetidinol

Ausbeute 48.4%

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONThereafter, 4.25 ml of a boron trifluoride-tetrahydrofuran complex was added dropwise
2. 2
   workup.WAITat 40° C. for 3 hours
3. 3
   TemperaturThereafter, the reaction solution was cooled to 10° C
4. 4
   Temperaturby reflux for 1 hour
5. 5
   TemperaturAfter cooling
6. 6
   Einengenthe solvent was concentrated under a reduced pressure, and ethyl acetate
7. 7
   workup.ADDITIONwas added
8. 8
   workup.ADDITIONThe pH of the mixture was adjusted to pH 9.4 by addition of a 20% aqueous sodium hydroxide solution
9. 9
   Sonstigean organic layer was then separated
10. 10
    WaschenThe organic layer was successively washed with water
11. 11
    Trocknena saturated saline solution, and then dried over anhydrous magnesium sulfate
12. 12
    workup.DISTILLATIONThe solvent was then distilled away under a reduced pressure
13. 13
    SonstigeThe residue was purified by column chromatography (eluent; chloroform:methanol=20:1 to 10:1)
14. 14
    Sonstigecrystallized from toluene-diisopropyl ether (1:3; 14 ml)

Vorschrift

5.00 g of 3-(2-(1-benzothiophene-5-yl)ethoxy)-1-(3-hydroxy-1-azetidinyl)-1-propanone was dissolved in 20 ml of tetrahydrofuran, and 1.09 g of sodium borohydride was then added thereto. Thereafter, 4.25 ml of a boron trifluoride-tetrahydrofuran complex was added dropwise thereto at 10° C., and the obtained mixture was then stirred at the same temperature for 1 hour and then at 40° C. for 3 hours. Thereafter, the reaction solution was cooled to 10° C. Thereafter, 30 ml of 6 mol/l hydrochloric acid was added dropwise to the reaction mixture, followed by reflux for 1 hour. After cooling, the solvent was concentrated under a reduced pressure, and ethyl acetate was added thereto. The pH of the mixture was adjusted to pH 9.4 by addition of a 20% aqueous sodium hydroxide solution, and an organic layer was then 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 purified by column chromatography (eluent; chloroform:methanol=20:1 to 10:1), and then crystallized from toluene-diisopropyl ether (1:3; 14 ml), so as to obtain 2.31 g of 1-(3-(2-(1-benzothiophene-5-yl)ethoxy)propyl)-3-azetidinol.

Quelle