Reaction #2464343

Reaction equation

3-[2-(1-benzothiophen-5-yl)ethoxy]propionic acid

thionyl chloride

3-hydroxyazetidine

1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}-3-azetidinol

sodium hydroxide

→

3-[2-(1-benzothiophen-5-yl)ethoxy]-1-(3-hydroxy-1-azetidinyl)-1-propanone

Yield 117.8%

Solvents

Ethyl acetate

N,N-dimethylformamide

water

toluene

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGstirred at room temperature for 1 hour
3. 3
   Otherthe organic layer was separated
4. 4
   WashThe organic layer was washed with diluted hydrochloric acid
5. 5
   Dryinga saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate
6. 6
   workup.DISTILLATIONdistilled under reduced pressure
7. 7
   Otherto remove the solvent
8. 8
   OtherThe residue was purified by a column chromatography (eluent; chloroform:acetone=3:1 to 1:1)
9. 9
   Othercrystallized from diisopropyl ether

Procedure

In 12.5 mL of toluene was suspended 5.00 g of 3-[2-(1-benzothiophen-5-yl)ethoxy]propionic acid, and 0.1 mL of N,N-dimethylformamide was added thereto, after which 1.68 mL of thionyl chloride was added dropwise thereto at 15° C. and the resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was added dropwise to a solution of 4.44 g of 3-hydroxyazetidine 1/2 tartrate and 3.76 g of sodium hydroxide in 25 mL of water at 10° C., and stirred at room temperature for 1 hour. Ethyl acetate was added to the reaction mixture and the organic layer was separated. The organic layer was washed with diluted hydrochloric acid and then a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to remove the solvent. The residue was purified by a column chromatography (eluent; chloroform:acetone=3:1 to 1:1) and crystallized from diisopropyl ether to obtain 5.48 g of 3-[2-(1-benzothiophen-5-yl)ethoxy]-1-(3-hydroxy-1-azetidinyl)-1-propanone as colorless crystals.

Source