Hydrochloric Acid → 1-(4-Aminobutyl)-4,4-diphenylpiperidine

HRID 396621Notes

Reaction equation

HRID 396621 reaction equation
[C:1]1([C:7]2([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][C:16]#[N:17])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.CCOCC>C1COCC1.C(Cl)Cl>[NH2:17][CH2:16][CH2:15][CH2:14][CH2:13][N:10]1[CH2:11][CH2:12][C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:8][CH2:9]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 230041164-(4,4-Diphenylpiperidin-1-yl)butyronitrile

Product 1

HCID 230041441-(4-Aminobutyl)-4,4-diphenylpiperidine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 4-(4,4-diphenylpiperidin-1-yl)butyronitrile (4.65 g, 15.3 mmol, 1.0 equiv) in anhydrous THF (20 mL) under argon was added a solution of BH3 in THF (1.0 M, 54 mL, 54 mmol, 3.5 equiv) at room temperature. The mixture was refluxed for 4.5 hours and then cooled to room temperature and concentrated to a volume of about 40 mL. Aqueous HCl (6 N, 55 mL) was added cautiously at 0° C. and stirring was continued for 2 hours at 55-65° C. The mixture was cooled to 0° C., basified to pH 10 by addition of 6 N aq. NaOH, and extracted with CH2Cl2 (3×100 mL). The combined organic solutions were dried over MgSO4 and concentrated. To a solution of the residue in CH2Cl2 (50 mL) was added HCl in ether (1.0 M, 30 mL, 2.0 equiv). After removal of the solvents, the residue was dissolved in CH2Cl2 (10 mL) and this solution was added dropwise into ether (150 mL) with swirling. The resulting solid was filtered and washed with ether (100 mL). This solid was taken up in water (30 mL), which was basified to pH 10 by addition of 1 M aqueous NaOH, and extracted with CH2Cl2 (3×50 mL). The combined organic solutions were dried over MgSO4 and concentrated to give 4.51 g (95%) of light brown oil, which was characterized spectroscopically.

Workup

  1. temperatureThe mixture was refluxed for 4.5 hours
  2. concentrationconcentrated to a volume of about 40 mL
  3. additionAqueous HCl (6 N, 55 mL) was added cautiously at 0° C.
  4. temperatureThe mixture was cooled to 0° C.
  5. additionbasified to pH 10 by addition of 6 N aq. NaOH
  6. extractionextracted with CH2Cl2 (3×100 mL)
  7. dry with materialThe combined organic solutions were dried over MgSO4
  8. concentrationconcentrated
  9. customAfter removal of the solvents
  10. dissolutionthe residue was dissolved in CH2Cl2 (10 mL)
  11. additionthis solution was added dropwise into ether (150 mL)
  12. filtrationThe resulting solid was filtered
  13. washwashed with ether (100 mL)
  14. additionwhich was basified to pH 10 by addition of 1 M aqueous NaOH
  15. extractionextracted with CH2Cl2 (3×50 mL)
  16. dry with materialThe combined organic solutions were dried over MgSO4
  17. concentrationconcentrated
  18. customto give 4.51 g (95%) of light brown oil, which

Sources & evidence

ORD record
ord-a24725a9485243ab9020525d64d2ada9
Source dataset
uspto-grants-2003_08
Patent number
US06608086B2

Reaction notes

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