Hydrochloric Acid → Edonerpic

HRID 597809

Reaction equation

HRID 597809 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]([N:17]3[CH2:20][CH:19]([OH:21])[CH2:18]3)=O)=[CH:9][C:4]=2[CH:3]=[CH:2]1.[BH4-].[Na+].Cl>O1CCCC1>[S:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][CH2:11][O:12][CH2:13][CH2:14][CH2:15][N:17]3[CH2:20][CH:19]([OH:21])[CH2:18]3)=[CH:9][C:4]=2[CH:3]=[CH:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 219900491-(3-(2-(1-Benzothiophen-5-yl)ethoxy)propionyl)azetidin-3-ol

Product 1

HCID 9901946EdonerpicYield 48.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

5.00 g of 3-(2-(1-benzothiophene-5-yl)ethoxy)-1-(3-hydroxy-1-azetidinyl)-1-propanone was dissolved in 20 ml of tetrahydrofuran, and 1.09 g of sodium borohydride was then added thereto. Thereafter, 4.25 ml of a boron trifluoride-tetrahydrofuran complex was added dropwise thereto at 10° C., and the obtained mixture was then stirred at the same temperature for 1 hour and then at 40° C. for 3 hours. Thereafter, the reaction solution was cooled to 10° C. Thereafter, 30 ml of 6 mol/l hydrochloric acid was added dropwise to the reaction mixture, followed by reflux for 1 hour. After cooling, the solvent was concentrated under a reduced pressure, and ethyl acetate was added thereto. The pH of the mixture was adjusted to pH 9.4 by addition of a 20% aqueous sodium hydroxide solution, and an organic layer was then separated. The organic layer was successively washed with water and a saturated saline solution, and then dried over anhydrous magnesium sulfate. The solvent was then distilled away under a reduced pressure. The residue was purified by column chromatography (eluent; chloroform:methanol=20:1 to 10:1), and then crystallized from toluene-diisopropyl ether (1:3; 14 ml), so as to obtain 2.31 g of 1-(3-(2-(1-benzothiophene-5-yl)ethoxy)propyl)-3-azetidinol.

Workup

  1. additionThereafter, 4.25 ml of a boron trifluoride-tetrahydrofuran complex was added dropwise
  2. waitat 40° C. for 3 hours
  3. temperatureThereafter, the reaction solution was cooled to 10° C
  4. temperatureby reflux for 1 hour
  5. temperatureAfter cooling
  6. concentrationthe solvent was concentrated under a reduced pressure, and ethyl acetate
  7. additionwas added
  8. additionThe pH of the mixture was adjusted to pH 9.4 by addition of a 20% aqueous sodium hydroxide solution
  9. customan organic layer was then separated
  10. washThe organic layer was successively washed with water
  11. dry with materiala saturated saline solution, and then dried over anhydrous magnesium sulfate
  12. distillationThe solvent was then distilled away under a reduced pressure
  13. customThe residue was purified by column chromatography (eluent; chloroform:methanol=20:1 to 10:1)
  14. customcrystallized from toluene-diisopropyl ether (1:3; 14 ml)

Sources & evidence

ORD record
ord-c56a2d28a59e410bba3e40676cc7a224
Source dataset
uspto-grants-2011_03
Patent number
US07897594B2

Linked notes

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