Ethylmorpholine → 4-(2-Benzyloxycarbonylamino-3-fluoro-butyryl)-piperazine-1-carboxylic acid propyl ester

HRID 1970573Notes

Reaction equation

HRID 1970573 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]([CH:16]([F:18])[CH3:17])[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:19]([O:22][C:23]([N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)=[O:24])[CH2:20][CH3:21].C(N1CCOCC1)C.[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O>CN(C=O)C.C(OCC)(=O)C>[CH2:19]([O:22][C:23]([N:25]1[CH2:30][CH2:29][N:28]([C:13](=[O:15])[CH:12]([NH:11][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH:16]([F:18])[CH3:17])[CH2:27][CH2:26]1)=[O:24])[CH2:20][CH3:21]

Participants

7

Reactant 4

HCID 7525EthylmorpholineHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 22393735Propyl piperazine-1-carboxylateHCID 668548062-Benzyloxycarbonylamino-3-fluoro-butyric acid

Product 1

HCID 668548184-(2-Benzyloxycarbonylamino-3-fluoro-butyryl)-piperazine-1-carboxylic acid propyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 500 mg 2-Benzyloxycarbonylamino-3-fluoro-butyric acid in 3 ml DMF were added 310 mg 1-propoxycarbonylpiperazine, 0.50 ml N-ethylmorpholine and 643 mg TOTU. After stirring for 12 h it was diluted with ethyl acetate and extracted with aqueous LiCl (4% w/w), aqueous NaHCO3, 0.1 M HCl and brine. The organic layer was dried over MgSO4 and concentrated to furnish the crude coupling product which was used without further purification in the next step. Yield: 591 mg

Workup

  1. extractionextracted with aqueous LiCl (4% w/w), aqueous NaHCO3, 0.1 M HCl and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated
  4. customto furnish the crude coupling product which
  5. customwas used without further purification in the next step

Sources & evidence

ORD record
ord-279bff66ce9c4b75838f84b3dfc0eff2
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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