Hydrochloric Acid → 1-(3-(2-(1-Benzothiophene-6-yl)ethoxy)propyl)-3-azetidinol

HRID 597807Notes

Reaction equation

HRID 597807 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][C:8]1[CH:16]=[CH:15][C:11]2[CH:12]=[CH:13][S:14][C:10]=2[CH:9]=1.Cl.[NH:18]1[CH2:21][CH:20]([OH:22])[CH2:19]1.C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O.C(OCC)(=O)C.O>[S:14]1[C:10]2[CH:9]=[C:8]([CH2:7][CH2:6][O:5][CH2:4][CH2:3][CH2:2][N:18]3[CH2:21][CH:20]([OH:22])[CH2:19]3)[CH:16]=[CH:15][C:11]=2[CH:12]=[CH:13]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 27592903-Hydroxyazetidine hydrochlorideHCID 219900846-(2-(3-Chloropropoxy)ethyl)-1-benzothiophene

Product 1

HCID 235455641-(3-(2-(1-Benzothiophene-6-yl)ethoxy)propyl)-3-azetidinolYield 24.5%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

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.

Workup

  1. waitat 95° C. for 1.5 hours
  2. temperatureThereafter, the reaction solution was cooled
  3. customa water layer was then separated
  4. additionEthyl acetate was added to the water layer
  5. additionthe pH of the obtained mixture was adjusted to pH 10 by addition of a 2 mol/l aqueous sodium hydroxide solution
  6. customfollowed by separation of an organic layer
  7. washThe organic layer was successively washed with water
  8. dry with materiala saturated saline solution, and then dried over anhydrous magnesium sulfate
  9. distillationThereafter, the solvent was distilled away under a reduced pressure
  10. customThe residue was purified by column chromatography (eluent; chloroform:methanol=30:1 to 5:1)

Sources & evidence

ORD record
ord-9f26211d9a8444fe8fcbcc5f4ce0cfb6
Source dataset
uspto-grants-2011_03
Patent number
US07897594B2

Reaction notes

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