Hydrochloric Acid → 1-(3-Aminopropyl)-4-cyclohexylpiperidine

HRID 322148Notes

Reaction equation

HRID 322148 reaction equation
[CH:1]1([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][C:15]#[N:16])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.CCOCC>C1COCC1>[NH2:16][CH2:15][CH2:14][CH2:13][N:10]1[CH2:9][CH2:8][CH:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 230041553-(4-Cyclohexylpiperidin-1-yl)propionitrile

Product 1

HCID 230041241-(3-Aminopropyl)-4-cyclohexylpiperidineYield 88.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 3-(4-cyclohexylpiperidin-1-yl)propionitrile (5.11 g, 23.3 mmol, 1.0 equiv) in anhydrous THF (15 mL) under argon was added a solution of BH3 in THF (1.0M, 82 mL, 3.5 equiv) at room temperature. The mixture was refluxed for 4.5 hours, then cooled to room temperature and concentrated to a volume of about 30 mL. Aqueous HCl (6N, 55 mL) was added and stirring was continued for 2 hours at 55-60° C. The mixture was basified to pH 9 by addition of 6N aq. NaOH and extracted with CH2Cl2 (3×100 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was dissolved in CH2Cl2 (20 mL) and treated with HCl in ether (1.0M, 58 mL, 2.5 equiv). The solvents were removed, ether (40 mL) was added, the mixture was filtered, and the filter cake was washed with ether (2×20 mL). Water (40 mL) was added to the resulting white solid, the pH was adjusted to 10 with 1M NaOH, and the aqueous phase was extracted with CH2Cl2 (3×80 mL). The combined organic solutions were dried over MgSO4 and concentrated to give 4.63 g (88%) of colorless oil, which was characterized spectroscopically.

Workup

  1. temperatureThe mixture was refluxed for 4.5 hours
  2. concentrationconcentrated to a volume of about 30 mL
  3. additionAqueous HCl (6N, 55 mL) was added
  4. additionThe mixture was basified to pH 9 by addition of 6N aq. NaOH
  5. extractionextracted with CH2Cl2 (3×100 mL)
  6. dry with materialThe combined organic solutions were dried over MgSO4
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in CH2Cl2 (20 mL)
  9. customThe solvents were removed
  10. additionether (40 mL) was added
  11. filtrationthe mixture was filtered
  12. washthe filter cake was washed with ether (2×20 mL)
  13. additionWater (40 mL) was added to the resulting white solid
  14. extractionthe aqueous phase was extracted with CH2Cl2 (3×80 mL)
  15. dry with materialThe combined organic solutions were dried over MgSO4
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-e4f9423f2cae4b1c8ec97605df36ecce
Source dataset
uspto-grants-2001_04
Patent number
US06211198B1

Reaction notes

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