5-tert-Butyl N-((phenylmethoxy)carbonyl)-L-glutamate → 4-((S)-2-Benzyloxycarbonylamino-4-tert-butoxycarbonyl-butyryl)-piperazine-1-carboxylic acid butyl ester

HRID 1185460Notes

Reaction equation

HRID 1185460 reaction equation
[C:1]([O:5][C:6](=[O:24])[CH2:7][CH2:8][C@H:9]([NH:13][C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C:10]([OH:12])=O)([CH3:4])([CH3:3])[CH3:2].[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.FC(F)(F)C(O)=O.[CH2:54]([O:58][C:59]([N:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1)=[O:60])[CH2:55][CH2:56][CH3:57]>CN(C=O)C.C(=O)([O-])O.[Na+]>[CH2:54]([O:58][C:59]([N:61]1[CH2:66][CH2:65][N:64]([C:10](=[O:12])[C@@H:9]([NH:13][C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:24])[CH2:63][CH2:62]1)=[O:60])[CH2:55][CH2:56][CH3:57]

Participants

6

Reactant 3

HCID 1074725-tert-Butyl N-((phenylmethoxy)carbonyl)-L-glutamateHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66854479Piperazine-1-carboxylic acid butyl ester trifluoroacetate

Product 1

HCID 451403594-((S)-2-Benzyloxycarbonylamino-4-tert-butoxycarbonyl-butyryl)-piperazine-1-carboxylic acid butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 22.4 g of (S)-2-Benzyloxycarbonylamino-pentanedioic acid 5-tert-butyl ester, 30.7 g of NEM and 21.8 g of TOTU in 75 ml of DMF, 20 g of Piperazine-1-carboxylic acid butyl ester trifluoroacetate was added at RT and stirred for 16 h. The reaction mixture was then diluted with saturated aqueous sodium hydrogen carbonate solution and then extracted with 300 ml of ethyl acetate. The organic phase was washed with diluted saturated aqueous sodium hydrogen carbonate solution and dried over MgSO4. The solvents were removed under reduced pressure. The crude product was purified by chromatography on silica gel eluting with n-heptane/ethyl acetate (1/1). The fractions containing the product were combined and the solvent evaporated under reduced pressure. Yield: 33.4 g.

Workup

  1. extractionextracted with 300 ml of ethyl acetate
  2. washThe organic phase was washed with diluted saturated aqueous sodium hydrogen carbonate solution
  3. dry with materialdried over MgSO4
  4. customThe solvents were removed under reduced pressure
  5. customThe crude product was purified by chromatography on silica gel eluting with n-heptane/ethyl acetate (1/1)
  6. additionThe fractions containing the product
  7. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-db1071ed94a14e3d883e2a7807b53b33
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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