Imidazole → Tert-butyl 3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(oxetan-3-yl)piperazine-1-carboxylate

HRID 921687Notes

Reaction equation

HRID 921687 reaction equation
[OH:1][CH2:2][CH:3]1[N:8]([CH:9]2[CH2:12][O:11][CH2:10]2)[CH2:7][CH2:6][N:5]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:4]1.N1C=CN=C1.[Si:25](Cl)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]>CN(C=O)C.CCOC(C)=O>[Si:25]([O:1][CH2:2][CH:3]1[N:8]([CH:9]2[CH2:12][O:11][CH2:10]2)[CH2:7][CH2:6][N:5]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:4]1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]

Participants

6

Reactant 3

HCID 795Imidazole2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 86708556(+/-) Tert-butyl 3-(hydroxymethyl)-4-(oxetan-3-yl)piperazine-1-carboxylate

Product 1

HCID 86708558Tert-butyl 3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(oxetan-3-yl)piperazine-1-carboxylateYield 46.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(+/−) Tert-butyl 3-(hydroxymethyl)-4-(oxetan-3-yl)piperazine-1-carboxylate (1 g, 3.67 mmol) was taken up in DMF (2 mL) and imidazole (0.500 g, 7.34 mmol) and TBS-Cl (0.609 g, 4.04 mmol) were added. The reaction was stirred at room temperature over the weekend. An additional 0.2 eq. of TBS-Cl and 0.5 eq. of imidazole were added, and the reaction mixture was heated at 40° C. overnight, then at 45° C. for 24 h. The reaction mixture was diluted with EtOAc and washed with water 4×. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-60% EtOAc/Hex). (+/−) Tert-butyl 3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(oxetan-3-yl)piperazine-1-carboxylate (665 mg) was obtained as a colorless oil.

Workup

  1. temperaturethe reaction mixture was heated at 40° C. overnight
  2. washwashed with water 4×
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe material was purified by flash column chromatography (0-60% EtOAc/Hex)

Sources & evidence

ORD record
ord-0024bd6d9a864c2ca3d780c1fe6232aa
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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