4-Benzyl-4-piperidinol → HCID 10098209, compound

HRID 1016651Notes

Reaction equation

HRID 1016651 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6]([C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)=[C:5]2[CH2:19][CH2:20][C:21]([OH:23])=O.[C:24]1([CH2:30][C:31]2([OH:37])[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6]([C:12]1[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=1)=[C:5]2[CH2:19][CH2:20][C:21]([N:34]1[CH2:33][CH2:32][C:31]([CH2:30][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([OH:37])[CH2:36][CH2:35]1)=[O:23]

Participants

4

Reactant 2

HCID 981524-Benzyl-4-piperidinolHCID 18669077HCID 18669077, compound

Product 1

HCID 10098209HCID 10098209, compoundYield 71.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1-Carbonyl diimidazole (47 mg, 0.29 mmol) was added to a solution of 5-chloro-2-(4-chlorophenyl)-1-methyl-1H-indole-3-propanoic acid (Description 31, 100 mg, 0.29 mmol) in tetrahydrofuran (4 mL) and the mixture was heated under reflux for 2 h. The mixture was cooled and 4-(phenylmethyl)-4-piperidinol (52 mg, 0.27 mmol) was added. The mixture was stirred at room temperature overnight and the solvent was evaporated under reduced pressure. Water (4 mL) was added and the mixture was stirred at 80° C. for 2 h. The mixture was cooled, the water was decanted and the residue was dissolved in dichloromethane. Using a Bond Elut™ cartridge to separate the layers the solution was washed with hydrochloric acid (1M), and aqueous sodium hydroxide (2M). The organic fraction was evaporated under reduced pressure to a small volume and filtered through a plug of silica on a Bond Elut™ cartridge, eluting with hexane/EtOAc (85:15 increasing to 70:30), to give the title compound as a colorless solid (101 mg, 68%). 1H NMR (360 MHz, CDCl3) δ 7.53 (1H, s), 7.40 (2H, d, J 6.5 Hz), 7.07-7.27 (9H, m), 4.29 (1H, m), 3.47 (3H, s), 3.29 (1H, m), 3.11 (1H, m), 2.90 (2H, m), 2.79 (1H, m), 2.59 (2H, s), 2.43 (2H, m), 1.52 (1H, br s), 1.40 (2H, m), 1.29 (1H, m), and 1.15 (1H, m). m/z (ES+) 521, 523 (M+1). Found: C, 69.30; H, 5.82; N, 5.36. C30H30Cl2N2O2 requires: C, 69.10; H, 5.80; N, 5.37%.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 h
  3. temperatureThe mixture was cooled
  4. customthe solvent was evaporated under reduced pressure
  5. additionWater (4 mL) was added
  6. stirringthe mixture was stirred at 80° C. for 2 h
  7. temperatureThe mixture was cooled
  8. customthe water was decanted
  9. dissolutionthe residue was dissolved in dichloromethane
  10. customto separate the layers the solution
  11. washwas washed with hydrochloric acid (1M), and aqueous sodium hydroxide (2M)
  12. customThe organic fraction was evaporated under reduced pressure to a small volume
  13. filtrationfiltered through a plug of silica on a Bond Elut™ cartridge
  14. washeluting with hexane/EtOAc (85:15 increasing to 70:30)

Sources & evidence

ORD record
ord-fc08bdd8a75b4c8e963a413cc98b5061
Source dataset
uspto-grants-2002_11
Patent number
US06476045B2

Reaction notes

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