Water → Benzyl tert-butyl piperazine-1,4-dicarboxylate

HRID 345418Notes

Reaction equation

HRID 345418 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH2:14]([O:21][C:22](Cl)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[OH-].[Na+].O>CC(C)=O>[C:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][N:11]([C:22]([O:21][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:23])[CH2:12][CH2:13]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

6

Reactant 4

HCID 962WaterHCID 10387Benzyl chloroformate2×HCID 14798Sodium Hydroxide2×HCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 15016698Benzyl tert-butyl piperazine-1,4-dicarboxylateYield 32.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To 15 g of BOC-piperazine (80.6 mmol) dissolved in acetone (50 ml) was added in alternating portions benzylchloroformate (11.5 ml, 80.6 mmol) and 1N NaOH (15 ml) keeping the pH at 8-8.5 and the temperature 0°-5° C. After 2 hours, starting material was still present (tlc) and an additional quantity of benzylchloroformate (5 ml) and 1N NaOH (5 ml) was added. The reaction mixture was aged at 5° C. overnight and at room temperature an additional 7 hours. Water was added and the mixture extracted with ethyl acetate (3×50 ml), dried with Na2SO4 and concentrated to 21 g of an oil. This oil was dissolved in 10 ml of ethyl acetate, passed through 40 ml of silica gel and eluted with 200 ml of ethylacetate. Crystallization was effected by trituration with petroleum ether and the crystals collected, affording 8.28 g (32%) of N-t-butoxycarbonyl-N'-benzyloxycarbonylpiperazine, m.p. 90.5°-91.5° C.

Workup

  1. additionwas added
  2. customthe temperature 0°-5° C
  3. waitThe reaction mixture was aged at 5° C. overnight and at room temperature an additional 7 hours
  4. extractionthe mixture extracted with ethyl acetate (3×50 ml)
  5. dry with materialdried with Na2SO4
  6. concentrationconcentrated to 21 g of an oil
  7. dissolutionThis oil was dissolved in 10 ml of ethyl acetate
  8. washeluted with 200 ml of ethylacetate
  9. customCrystallization
  10. customthe crystals collected

Sources & evidence

ORD record
ord-2f3d920bd91949d6998e1bddb2676d49
Source dataset
uspto-grants-1991_10
Patent number
US05057517

Reaction notes

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