Ninhydrin → Benzyloxycarbonyl-L-valyl-L-leucyl-L-threonine methyl ester

HRID 1732518Notes

Reaction equation

HRID 1732518 reaction equation
[CH3:1][O:2][C:3](=[O:27])[C@H:4]([C@@H:24]([CH3:26])[OH:25])[NH:5][C:6](=[O:23])[C@H:7]([CH2:19][CH:20]([CH3:22])[CH3:21])[NH:8]C(OCC1C=CC=CC=1)=O.CCN(C(C)C)C(C)C.[N+](C1C=CC(O[C:47](=[O:63])[C@H:48]([CH:60]([CH3:62])[CH3:61])[NH:49][C:50]([O:52][CH2:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[O:51])=CC=1)([O-])=O.C1C=CC2N(O)N=NC=2C=1.C1C=C2C(C(O)(O)C(=O)C2=CC=1)=O>CCO.Cl.[Pd]>[CH3:1][O:2][C:3](=[O:27])[C@H:4]([C@@H:24]([CH3:26])[OH:25])[NH:5][C:6](=[O:23])[C@H:7]([CH2:19][CH:20]([CH3:22])[CH3:21])[NH:8][C:47](=[O:63])[C@H:48]([CH:60]([CH3:61])[CH3:62])[NH:49][C:50]([O:52][CH2:53][C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1)=[O:51]

Participants

9

Reactant 5

HCID 10236NinhydrinHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 112124Z-Val-ONpHCID 54439782Benzyloxycarbonyl-L-leucyl-L-threonine methyl ester

Product 1

HCID 53923485Benzyloxycarbonyl-L-valyl-L-leucyl-L-threonine methyl ester

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent

Procedure

Benzyloxycarbonyl-L-leucyl-L-threonine methyl ester (I, 3.8 g, 10 mmole) was dissolved in a mixture of 95% EtOH (50 ml) and 1 N HCl (10 ml) and hydrogenated in the presence of a 10% Pd on charcoal catalyst (0.8 g). After removal of the catalyst and the solvent the residue was dissolved in DMF (35 ml), treated with DIEA (1.6 ml, 10 mmole), benzyloxycarbonyl-L-valine p-nitrophenyl ester (4.3 g, 12 mmole) and HOBt (1.5 g, 10 mmole). After a negative spot test with ninhydrin indicated the completion of the reaction, the solvent was removed in vacuo and the residue triturated with CHCl3 (40 ml). The resulting solid was washed with CHCl3 (20 ml) and dried: 4.5 g (94%, mp 217°-8° C.,) unchanged after extraction with solvents, [α]D24 -11.7° (c 1.5, DMF); RfC 0.75; Thr 1.08; Val 0.98; Leu 1.0.

Workup

  1. customAfter removal of the catalyst
  2. dissolutionthe solvent the residue was dissolved in DMF (35 ml)
  3. customthe completion of the reaction
  4. customthe solvent was removed in vacuo
  5. customthe residue triturated with CHCl3 (40 ml)
  6. washThe resulting solid was washed with CHCl3 (20 ml)
  7. customdried
  8. extraction4.5 g (94%, mp 217°-8° C.,) unchanged after extraction with solvents, [α]D24 -11.7° (c 1.5, DMF)

Sources & evidence

ORD record
ord-065fcdcd96ec4e4f8d0f437e82a1a642
Source dataset
uspto-grants-1980_12
Patent number
US04237046

Reaction notes

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