Sodium Hydroxide → 1-(3-(2-(1-Benzothiophen-5-yl)ethoxy)propionyl)azetidin-3-ol

HRID 2377161Notes

Reaction equation

HRID 2377161 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][CH2:11][O:12][CH2:13][CH2:14][C:15]([OH:17])=O)=[CH:9][C:4]=2[CH:3]=[CH:2]1.S(Cl)(Cl)=O.S1C2C=CC(CCOCCC[N:37]3[CH2:40][CH:39]([OH:41])[CH2:38]3)=CC=2C=C1.[OH-].[Na+]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C.CN(C)C=O>[S:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][CH2:11][O:12][CH2:13][CH2:14][C:15]([N:37]3[CH2:40][CH:39]([OH:41])[CH2:38]3)=[O:17])=[CH:9][C:4]=2[CH:3]=[CH:2]1

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 9901946EdonerpicHCID 219900803-(2-(1-Benzothiophen-5-yl)ethoxy)propionic acid

Product 1

HCID 219900491-(3-(2-(1-Benzothiophen-5-yl)ethoxy)propionyl)azetidin-3-olYield 117.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
15 °C

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.

Workup

  1. additionwas added
  2. stirringstirred at room temperature for 1 hour
  3. customthe organic layer was separated
  4. washThe organic layer was washed with diluted hydrochloric acid
  5. dry with materiala saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate
  6. distillationdistilled under reduced pressure
  7. customto remove the solvent
  8. customThe residue was purified by a column chromatography (eluent; chloroform:acetone=3:1 to 1:1)
  9. customcrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-389ee7bdaf6846aba5e3bea6e918aee5
Source dataset
uspto-grants-2008_12
Patent number
US07468443B2

Reaction notes

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