Hydrochloric Acid → T-817 maleate

HRID 553227Notes

Reaction equation

HRID 553227 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[Si](C)(C)C.Cl.[OH-:30].[Na+].[C:32]([O:35]CC)(=[O:34])[CH3:33]>O.COCCOCCOC>[C:19]([OH:21])(=[O:30])/[CH:20]=[CH:33]\[C:32]([OH:35])=[O:34].[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

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 219900491-(3-(2-(1-Benzothiophen-5-yl)ethoxy)propionyl)azetidin-3-ol

Product 1

HCID 11338749T-817 maleate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8150DiglymeSolvent

Conditions

Temperature
10 °C

Procedure

To bis(2-methoxyethyl)ether (5 mL) suspension of 1.00 g of 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propionyl)azetidin-3-ol was added 0.37 g of sodium borohydride, which was then cooled to 10° C. Thereto was dropwise added 2.49 mL of chlorotrimethylsilane at 5 to 10° C. for 20 minutes, which was then stirred at room temperature for 2.5 h and at 40° C. for 4 hours. After cooling, thereto was dropwise added 3.27 mL of 6.0 mol/L hydrochloric acid, which was then stirred at 70 to 75° C. for 30 minutes. To the reaction mixture were added water and ethyl acetate, and the pH was adjusted to 10.0 with 2.0 mol/L sodium hydroxide aqueous solution. The organic layer was separated, washed sequentially with water and saturated sodium chloride aqueous solution. Thereto were added anhydrous magnesium sulfate and activated carbon. After insoluble matter was filtered off, the solvent was distilled off under reduced pressure. To the resultant residue was added 0.36 g of maleic acid, which was solidified from a mixed solvent (5 mL) of ethyl acetate:2-propanol (4:1) to provide 0.72 g of 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol maleate as colorless crystal form.

Workup

  1. customat 5 to 10° C.
  2. customfor 20 minutes
  3. temperatureAfter cooling
  4. stirringwas then stirred at 70 to 75° C. for 30 minutes
  5. customThe organic layer was separated
  6. washwashed sequentially with water and saturated sodium chloride aqueous solution
  7. additionThereto were added anhydrous magnesium sulfate and activated carbon
  8. filtrationAfter insoluble matter was filtered off
  9. distillationthe solvent was distilled off under reduced pressure
  10. additionTo the resultant residue was added 0.36 g of maleic acid, which

Sources & evidence

ORD record
ord-69655022ea034829aecec9616631282b
Source dataset
uspto-grants-2011_05
Patent number
US07951963B2

Reaction notes

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