Imidazole → 4-Piperidineethanol TBS

HRID 876004Notes

Reaction equation

HRID 876004 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][OH:9])[CH2:3][CH2:2]1.[C:10]([Si:14](Cl)([CH3:16])[CH3:15])([CH3:13])([CH3:12])[CH3:11].N1C=CN=C1.C([O-])([O-])=O.[K+].[K+]>ClCCl>[Si:14]([O:9][CH2:8][CH2:7][CH:4]1[CH2:5][CH2:6][NH:1][CH2:2][CH2:3]1)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 11430Potassium Carbonate2×HCID 28928tert-Butyldimethylsilyl chlorideHCID 739534-Piperidineethanol

Product 1

HCID 162207594-Piperidineethanol TBSYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(piperidin-4-yl)ethanol (2.00 g, 15.5 mmol), t-butylchlorodimethylsilane (2.57 g, 17.0 mmol), and imidazole (1.05 g, 15.5 mmol) were taken up in dichloromethane (15 mL) and stirred for 22 hours. This solution was added to aqueous K2CO3 (80 mL) and extracted with dichloromethane (3×30 mL). The combined organics were dried (MgSO4) and evaporated to give a pale yellow oil. Silica gel chromatography (gradient elution dichloromethane+2.5% TEA/0-10% methanol) afforded a white solid. This solid was added to aqueous K2CO3 (60 mL) and extracted with dichloromethane+10% methanol (3×30 mL), the organics dried (MgSO4) and evaporated to give compound 292 as a yellow oil (3.24 g, 86%).

Workup

  1. extractionextracted with dichloromethane (3×30 mL)
  2. dry with materialThe combined organics were dried (MgSO4)
  3. customevaporated
  4. customto give a pale yellow oil
  5. washSilica gel chromatography (gradient elution dichloromethane+2.5% TEA/0-10% methanol)
  6. customafforded a white solid
  7. extractionextracted with dichloromethane+10% methanol (3×30 mL)
  8. dry with materialthe organics dried (MgSO4)
  9. customevaporated

Sources & evidence

ORD record
ord-4c27c03d82f543bc8904ec22e1c6d194
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

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