1-Piperazinecarboxylic acid, ethyl ester → 4-((S)-2-Benzyloxycarbonylamino-4-tert-butoxycarbonyl-butyryl)-piperazine-1-carboxylic acid ethyl ester

HRID 418046Notes

Reaction equation

HRID 418046 reaction equation
[NH:1]([C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])[C@H:2]([C:12]([OH:14])=O)[CH2:3][CH2:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH2:46]([O:48][C:49]([N:51]1[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1)=[O:50])[CH3:47].C([O-])(O)=O.[Na+]>C(Cl)Cl.C1COCC1.CC(=O)OCC>[CH2:46]([O:48][C:49]([N:51]1[CH2:52][CH2:53][N:54]([C:12](=[O:14])[C@@H:2]([NH:1][C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:3][CH2:4][C:5]([O:6][C:7]([CH3:8])([CH3:9])[CH3:10])=[O:11])[CH2:55][CH2:56]1)=[O:50])[CH3:47]

Participants

8

Reactant 5

HCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1074725-tert-Butyl N-((phenylmethoxy)carbonyl)-L-glutamateHCID 516892Sodium Bicarbonate

Product 1

HCID 666517784-((S)-2-Benzyloxycarbonylamino-4-tert-butoxycarbonyl-butyryl)-piperazine-1-carboxylic acid ethyl esterYield 98.9%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

To a solution of Z-(L)Glu(OtBu)-OH (5 g) in DCM/THF (1:1, 42 ml) were added at RT HOBT (2.5 g) and EDCI (3.1 g). After 15 min stirring at RT, 1-ethoxycarbonylpiperazine (2.6 g) was added and the stirring was continued at RT overnight. 150 ml of EA and 60 ml of a NaHCO3 solution were added to the reaction mixture and the phases were separated. The org. phase was washed with an aq. NaHSO4 (1M) solution and with brine, dried over Na2SO4 and evaporated off. After HV drying, 7 g of the desired compound were obtained.

Workup

  1. waitthe stirring was continued at RT overnight
  2. customthe phases were separated
  3. washphase was washed with an aq. NaHSO4 (1M) solution and with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated off
  6. customAfter HV drying

Sources & evidence

ORD record
ord-ab5337ab9c34419089794c0202e6fccf
Source dataset
uspto-grants-2012_01
Patent number
US08093250B2

Reaction notes

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