Imidazole → (R)-t-Butyl 2-((t-butyldimethylsilyloxy)methyl)piperazine-1-carboxylate

HRID 876012

Reaction equation

HRID 876012 reaction equation
[OH:1][CH2:2][C@H:3]1[CH2:8][NH:7][CH2:6][CH2:5][N:4]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].[C:16]([Si:20](Cl)([CH3:22])[CH3:21])([CH3:19])([CH3:18])[CH3:17].N1C=CN=C1.C([O-])([O-])=O.[K+].[K+]>ClCCl>[Si:20]([O:1][CH2:2][C@H:3]1[CH2:8][NH:7][CH2:6][CH2:5][N:4]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:22])[CH3:21]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 24820219(R)-2-Hydroxymethyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 58299667(R)-t-Butyl 2-((t-butyldimethylsilyloxy)methyl)piperazine-1-carboxylateYield 60.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-t-Butyl 2-(hydroxymethyl)piperazine-1-carboxylate (1.15 g, 5.32 mmol), t-butylchlorodimethylsilane (0.882 g, 5.85 mmol), and imidazole (0.796 g, 11.7 mmol) were stirred in dichloromethane (3 mL) for three days. The solution was added to aqueous K2CO3 (30 mL) and extracted with dichloromethane (3×30 mL). The combined organics were dried (MgSO4) and evaporated to give a yellow oil. Silica gel chromatography (gradient elution hexanes/0-50% ethyl acetate) afforded compound 308 as a colorless oil (1.06 g, 60%).

Workup

  1. extractionextracted with dichloromethane (3×30 mL)
  2. dry with materialThe combined organics were dried (MgSO4)
  3. customevaporated
  4. customto give a yellow oil
  5. washSilica gel chromatography (gradient elution hexanes/0-50% ethyl acetate)

Sources & evidence

ORD record
ord-7282317f085f4061830c5b73a88005a5
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Linked notes

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