tert-Butyl piperazine-1-carboxylate → 1,1-Dimethylethyl 2-(methylamino)-2-oxoethyl piperazine-1,4-dicarboxylate

HRID 1640409Notes

Reaction equation

HRID 1640409 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:14](=O)([O:21]C1C=CC([N+]([O-])=O)=CC=1)[O:15][CH2:16][C:17]([NH:19][CH3:20])=[O:18]>ClCCCl>[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][N:4]([C:14]([O:15][CH2:16][C:17]([NH:19][CH3:20])=[O:18])=[O:21])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 602095484-Nitrophenyl 2-(methylamino)-2-oxoethyl carbonate

Product 1

HCID 602095541,1-Dimethylethyl 2-(methylamino)-2-oxoethyl piperazine-1,4-dicarboxylateYield 71%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

A solution of 0.53 g (2.85 mmol) of 1,1-dimethylethyl 1-piperazinecarboxylate in 5 ml of 1,2-dichloroethane is added dropwise at about 0° C. to a solution, cooled to 0° C., of 1.1 g (3 mmol) of 2-(methylamino)-2-oxoethyl 4-nitrophenyl carbonate, prepared in step 2.2. of Example 2, in 10 ml of 1,2-dichloroethane. Stirring is continued at 0° C. for 1 hour, and then at room temperature for 3 hours. The reaction mixture is concentrated under reduced pressure and the residue thus obtained is purified by chromatography on silica gel, eluting with a 20/80 mixture of ethyl acetate and cyclohexane. The gradient is gradually increased to complete the elution with ethyl acetate. An oily residue that crystallizes from diisopropyl ether is obtained. 0.61 g of product is obtained in the form of a white solid, and is used without further purification in the following step.

Workup

  1. customprepared in step 2.2
  2. waitat room temperature for 3 hours
  3. concentrationThe reaction mixture is concentrated under reduced pressure
  4. customthe residue thus obtained
  5. customis purified by chromatography on silica gel
  6. washeluting with a 20/80 mixture of ethyl acetate and cyclohexane
  7. temperatureThe gradient is gradually increased
  8. washthe elution with ethyl acetate
  9. customAn oily residue that crystallizes from diisopropyl ether
  10. customis obtained

Sources & evidence

ORD record
ord-2322d19a11014bdba8ff0879fcc77de7
Source dataset
uspto-grants-2012_02
Patent number
US08114866B2

Reaction notes

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