Hydrochloric Acid → HCID 10728418, compound

HRID 396645Notes

Reaction equation

HRID 396645 reaction equation
[OH:1][C:2]1([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][C:10]#[N:11])[CH2:4][CH2:3]1.Cl.[OH-].[Na+].CCOCC>C1COCC1.C(Cl)Cl>[NH2:11][CH2:10][CH2:9][CH2:8][N:5]1[CH2:4][CH2:3][C:2]([OH:1])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 521362HCID 521362, compound

Product 1

HCID 10728418HCID 10728418, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(4-hydroxy-4-phenylpiperidin-1-yl)propionitrile (3.71 g, 16.1 mmol, 1.00 equiv) in THF (15 mL) at room temperature was added boranetetrahydrofuran complex (1.0 M in THF, 56.3 mL, 56.3 mmol, 3.50 equiv) dropwise. The mixture was stirred at reflux for 4.5 hours and then cooled to room temperature. Aqueous HCl (6 N, 85 mL) was added and the mixture was stirred at 50-70° C. for 2 hours. The mixture was basified to pH 9-10 by addition of 6 N aqueous NaOH and extracted with EtOAc (75 mL) and CH2Cl2 (3×75 mL). The combined organic solutions were dried over MgSO4 and concentrated. To a solution of the residue in CH2Cl2 (75 mL) was added HCl in Et2O (1.0 M, 38 mL, 2.3 equiv). After removal of the solvents, the residue was triturated with Et2O (185 mL). The resulting white solid was collected by filtration and washed with Et2O. Water (50 mL) was added to this solid, and the mixture was basified to pH 10-11 by addition of 1 N aqueous NaOH and extracted with CH2Cl2 (150 mL+2×75 mL). The combined CH2Cl2 solutions were dried over MgSO4 and concentrated to give 3.12 g (83%) of colorless oil, which was characterized spectroscopically.

Workup

  1. temperatureat reflux for 4.5 hours
  2. stirringthe mixture was stirred at 50-70° C. for 2 hours
  3. extractionextracted with EtOAc (75 mL) and CH2Cl2 (3×75 mL)
  4. dry with materialThe combined organic solutions were dried over MgSO4
  5. concentrationconcentrated
  6. customAfter removal of the solvents
  7. customthe residue was triturated with Et2O (185 mL)
  8. filtrationThe resulting white solid was collected by filtration
  9. washwashed with Et2O
  10. additionWater (50 mL) was added to this solid
  11. additionthe mixture was basified to pH 10-11 by addition of 1 N aqueous NaOH
  12. extractionextracted with CH2Cl2 (150 mL+2×75 mL)
  13. dry with materialThe combined CH2Cl2 solutions were dried over MgSO4
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-3dc3f3899f0a4159971ced9b4b83a733
Source dataset
uspto-grants-2003_08
Patent number
US06608086B2

Reaction notes

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