Acetone → 1-{2-[2-(1-Benzothiophen-6-yl)ethoxy]ethyl}-3-pyrrolidinol

HRID 597814Notes

Reaction equation

HRID 597814 reaction equation
[S:1]1[C:5]2[CH:6]=[C:7]([CH2:10][CH2:11][O:12][CH2:13][C:14]([N:16]3[CH2:20][CH2:19][CH:18]([OH:21])[CH2:17]3)=O)[CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.CC(C)=O.Cl.O>O1CCCC1.C(OCC)(=O)C>[S:1]1[C:5]2[CH:6]=[C:7]([CH2:10][CH2:11][O:12][CH2:13][CH2:14][N:16]3[CH2:20][CH2:19][CH:18]([OH:21])[CH2:17]3)[CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1

Participants

7

Reactant 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 962WaterHCID 219901402-(2-(1-Benzothiophene-6-yl)ethoxy)-1-(3-hydroxy-1-pyrrolidinyl)-1-ethanone

Product 1

HCID 219900201-{2-[2-(1-Benzothiophen-6-yl)ethoxy]ethyl}-3-pyrrolidinol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

The above 2-(2-(1-benzothiophene-6-yl)ethoxy)-1-(3-hydroxy-1-pyrrolidinyl)-1-ethanone was dissolved in 7.4 ml of tetrahydrofuran. Thereafter, 7.4 ml of a tetrahydrofuran solution containing a 1 mol/l borane-tetrahydrofuran complex was added dropwise to the obtained solution while cooling on ice, and the obtained mixture was then stirred at a room temperature for 17 hours. Thereafter, 10 ml of acetone was added to the reaction mixture, and the obtained mixture was then stirred for 30 minutes. Thereafter, 1.5 ml of 6 mol/l hydrochloric acid was added thereto, and the obtained mixture was heated to reflux for 2 hours. After the reaction mixture was cooled, water and ethyl acetate were added thereto, and a water layer was separated. Thereafter, ethyl acetate was added to the water layer. The pH of the obtained mixture was adjusted to pH 9.5 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 20:1), so as to obtain 0.53 g of a yellow oil product, 1-(2-(2-(1-benzothiophene-6-yl)ethoxy)ethyl)-3-pyrrolidinol.

Workup

  1. additionwas added dropwise to the obtained solution
  2. temperaturewhile cooling on ice
  3. stirringthe obtained mixture was then stirred for 30 minutes
  4. temperaturethe obtained mixture was heated
  5. temperatureto reflux for 2 hours
  6. temperatureAfter the reaction mixture was cooled
  7. customa water layer was separated
  8. additionThereafter, ethyl acetate was added to the water layer
  9. additionThe pH of the obtained mixture was adjusted to pH 9.5 by addition of a 2 mol/l aqueous sodium hydroxide solution
  10. customfollowed by separation of an organic layer
  11. washThe organic layer was successively washed with water
  12. dry with materiala saturated saline solution, and then dried over anhydrous magnesium sulfate
  13. distillationThereafter, the solvent was distilled away under a reduced pressure
  14. customThe residue was purified by column chromatography (eluent; chloroform:methanol=30:1 to 20:1)

Sources & evidence

ORD record
ord-28b7bb73887c44fab5b70b8d79bf1b52
Source dataset
uspto-grants-2011_03
Patent number
US07897594B2

Reaction notes

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