Hydrochloric Acid → T-817 maleate

HRID 2390984Notes

Reaction equation

HRID 2390984 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+].F[C:25](F)(F)[C:26]([OH:28])=[O:27].Cl.[C:32]([O:35]CC)(=[O:34])[CH3:33]>O.O1CCCC1>[C:26]([OH:28])(=[O:27])/[CH:25]=[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

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 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 8028TetrahydrofuranSolvent2×

Procedure

To tetrahydrofuran (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, and dropwise added tetrahydrofuran (1 mL) solution of 0.75 mL of trifluoroacetic acid for 30 minutes, which was then refluxed for 2 hours. After cooling, thereto was dropwise added 3.27 mL of 6.0 mol/L hydrochloric acid, which was then refluxed for 1.5 hours. To the reaction mixture were added water and ethyl acetate, and the aqueous layer was separated. To the aqueous layer was added ethyl acetate, and the pH was adjusted to 10.0 with 20% (w/w) sodium hydroxide aqueous solution. The organic layer was separated, washed sequentially with water and saturated sodium chloride aqueous solution, and dried over anhydrous magnesium sulfate. 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 0.62 g of 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol maleate as colorless crystal form.

Workup

  1. temperaturewhich was then refluxed for 2 hours
  2. temperatureAfter cooling
  3. temperaturewas then refluxed for 1.5 hours
  4. customthe aqueous layer was separated
  5. additionTo the aqueous layer was added ethyl acetate
  6. customThe organic layer was separated
  7. washwashed sequentially with water and saturated sodium chloride aqueous solution
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationAfter insoluble matter was filtered off
  10. distillationthe solvent was distilled off under reduced pressure
  11. additionTo the resultant residue was added 0.36 g of maleic acid, which

Sources & evidence

ORD record
ord-df995eb59ac74caab103d48ecfc3b254
Source dataset
uspto-grants-2012_09
Patent number
US08273902B2

Reaction notes

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