Hydrochloric Acid → (R)-1-(2-benzothienyl)-2-propylaminopentane hydrochloride

HRID 1158248Notes

Reaction equation

HRID 1158248 reaction equation
C([Li])CCC.[S:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[CH:8]=[CH:7]1.[CH2:15]([N:18]1[C@H:22]([CH2:23][CH2:24][CH3:25])[CH2:21]OS1(=O)=O)[CH2:16][CH3:17].[ClH:28]>O1CCCC1.C(OCC)C.COCCOC.CCCCCC>[ClH:28].[S:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[CH:8]=[C:7]1[CH2:21][C@H:22]([NH:18][CH2:15][CH2:16][CH3:17])[CH2:23][CH2:24][CH3:25]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 7221Benzo(B)ThiopheneHCID 86630301(R)-3,4-Dipropyl-1,2,3-oxathiazolidine 2,2-dioxideHCID 178418339Butyllithium

Product 1

HCID 67425574(R)-1-(2-benzothienyl)-2-propylaminopentane hydrochlorideYield 70%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Under an argon atmosphere, n-butyl lithium (a 1.56 mol/L hexane solution, 44.4 mL) and 1,2-dimethoxyethane (7.2 mL) were added to a solution of benzothiophene (8.45 g) in tetrahydrofuran (120 mL) under ice-cooling and stirring and then stirred under ice-cooling for 30 minutes. A solution of (R)-3,4-dipropyl-1,2,3-oxathiazolidine 2,2-dioxide (14.36 g) in tetrahydrofuran (43.0 mL) was added dropwise to the resulting solution and stirred under ice-cooling for 2.5 hours. Under ice-cooling and stirring, 1 mol/L hydrochloric acid (200 mL) was added to the resulting solution and stirred at room temperature for 1.5 hours. Diethyl ether (200 mL) was added to the solution, and the mixture was separated. The aqueous layer was neutralized with 1 mol/L sodium hydroxide and then extracted with diethyl ether. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. Saturated hydrogen chloride in diethyl ether (10 mL) was added to a solution of the residue in diethyl ether (50 mL) under ice-cooling and stirring. After stirring at the same temperature for several minutes, the solvent was removed under reduced pressure. The residue was recrystallized from ethanol (100 mL) to give (R)-1-(2-benzothienyl)-2-propylaminopentane hydrochloride (13.17 g, 70% yield) as white crystals.

Workup

  1. temperaturecooling
  2. stirringstirred under ice-
  3. temperaturecooling for 30 minutes
  4. stirringstirred under ice-
  5. temperaturecooling for 2.5 hours
  6. temperatureUnder ice-cooling
  7. stirringstirring
  8. stirringstirred at room temperature for 1.5 hours
  9. customthe mixture was separated
  10. extractionextracted with diethyl ether
  11. washThe organic layer was washed with water
  12. dry with materiala saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate
  13. concentrationconcentrated under reduced pressure
  14. additionSaturated hydrogen chloride in diethyl ether (10 mL) was added to a solution of the residue in diethyl ether (50 mL) under ice-
  15. temperaturecooling
  16. stirringstirring
  17. stirringAfter stirring at the same temperature for several minutes
  18. customthe solvent was removed under reduced pressure
  19. customThe residue was recrystallized from ethanol (100 mL)

Sources & evidence

ORD record
ord-fe41558262d84ca3a4ba35e6cc880fbd
Source dataset
uspto-grants-2010_10
Patent number
US07807840B2

Reaction notes

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