Trifluoroacetic acid → 4-((R)-2-Amino-3-fluoro-propionyl)-piperazine-1-carboxylic acid ethyl ester

HRID 1970633Notes

Reaction equation

HRID 1970633 reaction equation
C(OC([NH:8][C@@H:9]([CH2:13][F:14])[C:10](O)=[O:11])=O)(C)(C)C.[CH2:15]([O:17][C:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)=[O:19])[CH3:16].C(N1CCOCC1)C.[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.C(O)(C(F)(F)F)=O>CN(C=O)C.C(OCC)(=O)C.ClCCl>[CH2:15]([O:17][C:18]([N:20]1[CH2:21][CH2:22][N:23]([C:10](=[O:11])[C@@H:9]([NH2:8])[CH2:13][F:14])[CH2:24][CH2:25]1)=[O:19])[CH3:16]

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7525EthylmorpholineHCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 13105160(2R)-2-{[(tert-butoxy)carbonyl]amino}-3-fluoropropanoic acid

Product 1

HCID 668553184-((R)-2-Amino-3-fluoro-propionyl)-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 150 mg (R)-tert-butoxycarbonylamino-3-fluoropropionic acid in 2 ml DMF were added 115 mg 1-ethoxycarbonylpiperazine, 0.18 ml N-ethylmorpholine and 238 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 deprotected by using 10 equivalents TFA in dichloromethane. After stirring for 12 h it was concentrated and codistilled twice with toluene. Yield: 216 mg colorless oil.

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. stirringAfter stirring for 12 h it
  6. concentrationwas concentrated

Sources & evidence

ORD record
ord-077cfc79b074459ca338f5ca0d353e16
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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