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

HRID 553809Notes

Reaction equation

HRID 553809 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=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl.[CH2:48]([O:50][C:51]([N:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1)=[O:52])[CH3:49].C([O-])(O)=O.[Na+]>C(Cl)Cl.C1COCC1.CC(=O)OCC>[CH2:48]([O:50][C:51]([N:53]1[CH2:54][CH2:55][N:56]([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])[CH2:57][CH2:58]1)=[O:52])[CH3:49]

Participants

8

Reactant 5

HCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 1074725-tert-Butyl N-((phenylmethoxy)carbonyl)-L-glutamateHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrate

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

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

Workup

  1. waitthe stirring was continued overnight at RT
  2. customthe phases were separated
  3. washphase was washed with 60 ml of a 1M NaHSO4 solution and 60 ml of a NaCl solution
  4. dry with materialwas dried (Na2SO4)
  5. customevaporated off
  6. customAfter HV drying

Sources & evidence

ORD record
ord-c4e52ecc6914452199f3fdb39621761c
Source dataset
uspto-grants-2011_11
Patent number
US08048881B2

Reaction notes

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