Hydrochloric Acid → T-817 maleate

HRID 2390985Notes

Reaction equation

HRID 2390985 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+].S(OC)(OC)(=O)=[O:25].Cl.[OH-].[Na+].[C:34]([O:37]CC)(=[O:36])[CH3:35]>O1CCCC1>[C:19]([OH:21])(=[O:25])/[CH:20]=[CH:35]\[C:34]([OH:37])=[O:36].[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 6

HCID 313Hydrochloric AcidHCID 6497Dimethyl SulfateHCID 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 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To tetrahydrofuran (3 mL) suspension of 0.50 g of 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propionyl)azetidin-3-ol was added 0.19 g of sodium borohydride, which was then heated to 50° C. Thereto was dropwise added tetrahydrofuran (1 mL) solution of 0.46 mL of dimethyl sulfate at 50 to 55° C. for 10 minutes, which was then stirred at same temperature for 2.5 hours. After cooling, thereto was dropwise added 1.64 mL of 6.0 mol/L hydrochloric acid, which was then refluxed for 1.5 hours. To the reaction mixture 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 0.18 g of maleic acid, which was solidified from a mixed solvent (3.75 mL) of ethyl acetate:2-propanol (4:1) to provide 0.49 g of 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol maleate as colorless crystal form.

Workup

  1. customat 50 to 55° C.
  2. customfor 10 minutes
  3. temperatureAfter cooling
  4. temperaturewas then refluxed for 1.5 hours
  5. customThe organic layer was separated
  6. washwashed sequentially with water and saturated sodium chloride aqueous solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationAfter insoluble matter was filtered off
  9. distillationthe solvent was distilled off under reduced pressure
  10. additionTo the resultant residue was added 0.18 g of maleic acid, which

Sources & evidence

ORD record
ord-11dc55bc84b44bfbb0bd02e1022944f2
Source dataset
uspto-grants-2012_09
Patent number
US08273902B2

Reaction notes

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