Hydrochloric Acid → T-817 maleate

HRID 2390983Notes

Reaction equation

HRID 2390983 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.COCCOC>[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 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
10 °C

Procedure

To 1,2-dimethoxyethane (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., 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 0.71 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. temperatureAfter cooling
  3. stirringwas then stirred at 70 to 75° C. for 30 minutes
  4. customThe organic layer was separated
  5. washwashed sequentially with water and saturated sodium chloride aqueous solution
  6. additionThereto were added anhydrous magnesium sulfate and activated carbon
  7. filtrationAfter insoluble matter was filtered off
  8. distillationthe solvent was distilled off under reduced pressure
  9. additionTo the resultant residue was added 0.36 g of maleic acid, which

Sources & evidence

ORD record
ord-48b6028846a54193a0a67e05a89ffa5e
Source dataset
uspto-grants-2012_09
Patent number
US08273902B2

Reaction notes

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