Imidazole → 4-{[(Tert-butyldimethylsilyl)oxy]methyl}piperidine

HRID 875999Notes

Reaction equation

HRID 875999 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][OH:8])[CH2:3][CH2:2]1.[C:9]([Si:13](Cl)([CH3:15])[CH3:14])([CH3:12])([CH3:11])[CH3:10].N1C=CN=C1.C([O-])(O)=O.[Na+].[OH-].[Na+]>ClCCl>[Si:13]([O:8][CH2:7][CH:4]1[CH2:5][CH2:6][NH:1][CH2:2][CH2:3]1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:15])[CH3:14]

Participants

7

Reactant 5

HCID 795ImidazoleHCID 14798Sodium HydroxideHCID 28928tert-Butyldimethylsilyl chlorideHCID 4207714-PiperidinemethanolHCID 516892Sodium Bicarbonate

Product 1

HCID 670219944-{[(Tert-butyldimethylsilyl)oxy]methyl}piperidineYield 95.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Piperidin-4-ylmethanol (2.50 g, 21.7 mmol), t-butylchlorodimethylsilane (4.13 g, 23.9 mmol), and imidazole (1.48 g, 21.7 mmol) were dissolved in dichloromethane (25 mL) and stirred at room temperature for 18 hours. The reaction was added to aqueous NaHCO3 (200 mL, 50% saturated) and extracted with dichloromethane (3×150 mL). The combined organics were dried (MgSO4) and evaporated to give a yellow oil. Silica gel chromatography (gradient elution dichloromethane+2.5% TEA/0-10% methanol) gave a soft white solid, which was then added to 0.5 M NaOH (100 mL) and extracted with dichloromethane+10% methanol (3×100 mL). The combined organics were dried (MgSO4) and evaporated to give compound 284 as a pale yellow oil (4.75 g).

Workup

  1. extractionextracted with dichloromethane (3×150 mL)
  2. dry with materialThe combined organics were dried (MgSO4)
  3. customevaporated
  4. customto give a yellow oil
  5. washSilica gel chromatography (gradient elution dichloromethane+2.5% TEA/0-10% methanol)
  6. customgave a soft white solid, which
  7. extractionextracted with dichloromethane+10% methanol (3×100 mL)
  8. dry with materialThe combined organics were dried (MgSO4)
  9. customevaporated

Sources & evidence

ORD record
ord-c77b6a2813dd451d89174c5b81542e09
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

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