Reaction #1885063

ord-245117e4a2324fe4b9dadbccc2581d75

Reaction equation

CC(C)[C@@H](C(=O)ON1C(=O)CCC1=O)N(C)C(=O)OCC1c2ccccc2-c2ccccc21
Fmoc-MeVal-OSu
NC(=O)NCCC[C@H](N)C(=O)O
L-citrulline
O=C([O-])O.[Na+]
NaHCO3
→
CC(C)[C@@H](C(=O)N[C@@H](CCCNC(N)=O)C(=O)O)N(C)C(=O)OCC1c2ccccc2-c2ccccc21
Fmoc-MeVal-Cit-COOH
Yield 81.3%

Reactants

CC(C)[C@@H](C(=O)ON1C(=O)CCC1=O)N(C)C(=O)OCC1c2ccccc2-c2ccccc21
Fmoc-MeVal-OSu
NC(=O)NCCC[C@H](N)C(=O)O
L-citrulline
O=C([O-])O.[Na+]
NaHCO3

Reagents

None

Solvents

COCCOC
DME
C1CCOC1
THF
O
H2O

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Extractionit is extracted into tert-BuOH/CHCl3/H2O
  2. 2
    OtherThe organic phase is separated
  3. 3
    Otherdried
  4. 4
    Concentrationconcentrated under reduced pressure
  5. 5
    OtherThe residue is triturated with diethyl ether

Procedure

To a room temperature suspension of Fmoc-MeVal-OSu (2.18 g, 4.84 mmol) in DME (13 mL) and THF (6.5 mL) is added a solution of L-citrulline (0.85 g, 4.84 mmol) and NaHCO3 (0.41 g, 4.84 mmol) in H2O (13 mL). The suspension is allowed to stir at room temperature for 16 hr, then it is extracted into tert-BuOH/CHCl3/H2O and acidified to pH=2-3 with 1 M HCl. The organic phase is separated, dried and concentrated under reduced pressure. The residue is triturated with diethyl ether resulting Fmoc-MeVal-Cit-COOH (e.g., 2.01 g) which is used without further purification.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08343928B2uspto-grants-2013_01