Imidazole → HCID 11232313, compound

HRID 977300Notes

Reaction equation

HRID 977300 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Si:15](Cl)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16].N1C=CN=C1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 11232313HCID 11232313, compoundYield 92.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1-(tert-butyloxycarbonyl)-4-piperidinol (5.2 g, 25.9 mmol), tert-butyldimethylsilyl chloride (4.07 g, 1.05 equiv.) and imidazole (2.7 g, 1.5 equiv.) in DMF (20 mL) was stirred for 16 h. After dilution with Et2O, the solution was washed successively with H2O (2×), 10% aqueous citric acid, a saturated aqueous solution of NaHCO3 and brine. The organic layer was dried (MgSO4) and concentrated to dryness. The residue was purified by HPLC using a WATERS® LC-500 preparative chromatography apparatus [2 SiO2 columns: hexane-EtOAc (19:1), Millipore Corporation, Milford, Mass., USA] to give 1-(tert-butyloxycarbonyl)-4-(tert-butyldimethylsiloxy)piperidine (7.54 g, 92%). 1H NMR (CDCl3) δ3.87 (m, 1H), 3.61 (ddd, J=3.5, 7.5, 13.0 Hz, 2H), 3.24 (ddd, J=3.7, 8.0, 13.0 Hz, 2H), 1.48 (s, 9H), 0.88 (s, 9H), 0.07 (s, 6H).

Workup

  1. washAfter dilution with Et2O, the solution was washed successively with H2O (2×), 10% aqueous citric acid
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated to dryness
  4. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-cd680aa462414f929c8b8d0f24b1c3aa
Source dataset
uspto-grants-1997_03
Patent number
US05614533

Reaction notes

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