Hydrochloric Acid → Edonerpic

HRID 2377162Notes

Reaction equation

HRID 2377162 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

In 20 mL of tetrahydrofuran was dissolved 5.00 g of 3-[2-(1-benzothiophen-5-yl)ethoxy]-1-(3-hydroxy-1-azetidinyl)-1-propanone, and 1.09 g of sodium borohydride was added thereto, after which 4.25 mL of a boron trifluoride-tetrahydrofuran complex was added dropwise thereto at 10° C. and the resulting mixture was stirred at the same temperature for 1 hour and then at 40° C. for 3 hours. After the reaction mixture was cooled to 10° C., 30 mL of 6 mol/L hydrochloric acid was added dropwise thereto and the resulting mixture was refluxed for 1 hour. After cooling, the solvent was concentrated under reduced pressure, and ethyl acetate was added. The pH was adjusted to 9.4 with a 20% aqueous sodium hydroxide solution and then the organic layer was separated. The organic layer was washed with water and then a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to remove the solvent. The resulting residue was purified by a column chromatography (eluent; chloroform:methanol=20:1 to 10:1) and crystallized from toluene-diisopropyl ether (1:3, 14 mL) to obtain 2.31 g of 1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}-3-azetidinol.

Workup

  1. additionwas added
  2. additionafter which 4.25 mL of a boron trifluoride-tetrahydrofuran complex was added dropwise
  3. waitat 40° C. for 3 hours
  4. temperatureAfter the reaction mixture was cooled to 10° C.
  5. temperaturethe resulting mixture was refluxed for 1 hour
  6. temperatureAfter cooling
  7. concentrationthe solvent was concentrated under reduced pressure, and ethyl acetate
  8. additionwas added
  9. customthe organic layer was separated
  10. washThe organic layer was washed with water
  11. dry with materiala saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate
  12. distillationdistilled under reduced pressure
  13. customto remove the solvent
  14. customThe resulting residue was purified by a column chromatography (eluent; chloroform:methanol=20:1 to 10:1)
  15. customcrystallized from toluene-diisopropyl ether (1:3, 14 mL)

Sources & evidence

ORD record
ord-b88e9df6da2a4e6b95e9e8a0b999131b
Source dataset
uspto-grants-2008_12
Patent number
US07468443B2

Reaction notes

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