Reaction #684989

Reaction equation

hydrochloric acid

3-azetidinol hydrochloride

potassium carbonate

6-(2-(3-chloropropoxy)ethyl)-1-benzothiophene

→

achromatic oil

Yield 24.5%

1-(3-(2-(1-benzothiophene-6-yl)ethoxy)propyl)-3-azetidinol

Yield 24.5%

Solvents

dimethyl sulfoxide

ethyl acetate

water

Conditions

Workup

1. 1
   workup.WAITat 95° C. for 1.5 hours
2. 2
   TemperatureThereafter, the reaction solution was cooled
3. 3
   Othera water layer was then separated
4. 4
   workup.ADDITIONEthyl acetate was added to the water layer
5. 5
   workup.ADDITIONthe pH of the obtained mixture was adjusted to pH 10 by addition of a 2 mol/l aqueous sodium hydroxide solution
6. 6
   Otherfollowed by separation of an organic layer
7. 7
   WashThe organic layer was successively washed with water
8. 8
   Dryinga saturated saline solution, and then dried over anhydrous magnesium sulfate
9. 9
   workup.DISTILLATIONThereafter, the solvent was distilled away under a reduced pressure
10. 10
    OtherThe residue was purified by column chromatography (eluent; chloroform:methanol=30:1 to 5:1)

Procedure

1.00 g of 6-(2-(3-chloropropoxy)ethyl)-1-benzothiophene was dissolved in 5 ml of dimethyl sulfoxide. Thereafter, 0.86 g of 3-azetidinol hydrochloride and 1.63 g of potassium carbonate were added to the obtained solution, and the obtained mixture was stirred at 75° C. for 2.5 hours, and then at 95° C. for 1.5 hours. Thereafter, the reaction solution was cooled, and 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 a water layer was then separated. Ethyl acetate was added to the water layer, and the pH of the obtained mixture was adjusted to pH 10 by addition of a 2 mol/l aqueous sodium hydroxide solution, followed by separation of an organic layer. The organic layer was successively washed with water and a saturated saline solution, and then dried over anhydrous magnesium sulfate. Thereafter, the solvent was distilled away under a reduced pressure. The residue was purified by column chromatography (eluent; chloroform:methanol=30:1 to 5:1), so as to obtain 0.28 g of an achromatic oil product, 1-(3-(2-(1-benzothiophene-6-yl)ethoxy)propyl)-3-azetidinol.

Source