Dicyclohexylcarbodiimide → HCID 13769326, compound

HRID 1249298Notes

Reaction equation

HRID 1249298 reaction equation
[NH:1](C(OCC1C=CC=CC=1)=O)[C@@H:2]([C:4]([NH:6][CH2:7][C:8]([O:10][CH3:11])=[O:9])=[O:5])[CH3:3].[NH:22]([C:35]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36])[C@H:23]([C:32]([OH:34])=O)[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CO.C1COCC1.[Pd]>[NH:22]([C:35]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36])[C@H:23]([C:32]([NH:1][C@@H:2]([C:4]([NH:6][CH2:7][C:8]([O:10][CH3:11])=[O:9])=[O:5])[CH3:3])=[O:34])[CH2:24][C:25]1[CH:26]=[CH:27][C:28]([OH:31])=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 712438N-benzyloxycarbonyl-l-tyrosineHCID 2060367HCID 2060367, compound

Product 1

HCID 13769326HCID 13769326, compoundYield 94,212.5%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of Z-D-Ala-Gly-OMe (26) (5.88 g, 0.02 mmol) and 10% Pd-C (0.4 g) in methanol (300 ml) was stirred under a hydrogen atmosphere at room temperature for 1.5 hr. The catalyst was filtered and the filtrate was evaporated in vacuo. The residue and Z-Tyr (6.30 g, 0.02 mol) was dissolved in dry THF (300 ml), cooled to 0° C. and HOBt (2.70 g, 0.02 mol) and DCC (4.12 g. 0.02 mol) were added successively at 0° C. The solution was stirred for 3 hr at 0° C. and overnight at room temperature. The precipitated crystals were filtered. The filtrate was evaporated under reduced pressure, the residual crystals were dissolved in EtOAc and the solution was washed with 5% NaHCO3, 0.2 N Hcl and water, and dried over anhyd. Na2SO4. The solvent was removed in vacuo and the resulting solid was purified by silica gel column chromatography using CHCl3 --CH3OH (98:2) as eluant to give Z-Tyr-D-Ala-Gly-OMe (27) (8.62 g, 94.3%), mp 154°-155° C. (AcOEt-hexane); [α]D22 33.4° (C=1.0, MeOH); NMR (CDCl3 -DMSO-d6 (4:1) δ: 1.25 (3H, d, J=7 Hz, CH3), 2.82-3.03 (2H, m, CH2,), 3.70 (3H, s, CH3O), 3.80-3.95 (2H, m, CH2PhOH), 4.15-4.60 (2H, m, 2 CH), 5.05 (2H, s, CH2O), 6.70-7.25 (4H, m, ArH), 6.70-6.90 (1H, br, NH), 7.36 (5H, s, ArH), 7.70-8.10 (2H, br, NH). Rf (I)=0.48; Rf (VI)=0.08.

Workup

  1. filtrationThe catalyst was filtered
  2. customthe filtrate was evaporated in vacuo
  3. temperaturecooled to 0° C.
  4. stirringThe solution was stirred for 3 hr at 0° C. and overnight at room temperature
  5. filtrationThe precipitated crystals were filtered
  6. customThe filtrate was evaporated under reduced pressure
  7. dissolutionthe residual crystals were dissolved in EtOAc
  8. washthe solution was washed with 5% NaHCO3, 0.2 N Hcl and water
  9. customdried over anhyd
  10. customThe solvent was removed in vacuo
  11. customthe resulting solid was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-1c6945b078f749e9a2312d879f292d1c
Source dataset
uspto-grants-1986_12
Patent number
US04629784

Reaction notes

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