Methanol → Nalpha-Benzyloxycarbonyl-histidyl-D-tryptophyl-alanine

HRID 1109820Notes

Reaction equation

HRID 1109820 reaction equation
C[O:2][C:3](=[O:41])[C@H:4]([CH3:40])[NH:5][C:6](=[O:39])[C@@H:7]([CH2:29][C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[NH:32][CH:31]=1)[NH:8][C:9](=[O:28])[C@H:10]([CH2:22][C:23]1[N:27]=[CH:26][NH:25][CH:24]=1)[NH:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13].CO.[OH-].[Na+]>CO.O>[CH2:15]([O:14][C:12]([NH:11][C@H:10]([C:9]([NH:8][C@@H:7]([C:6]([NH:5][C@H:4]([C:3]([OH:41])=[O:2])[CH3:40])=[O:39])[CH2:29][C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[NH:32][CH:31]=1)=[O:28])[CH2:22][C:23]1[N:27]=[CH:26][NH:25][CH:24]=1)=[O:13])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 178501483Nalpha-Benzyloxycarbonyl-histidyl-D-tryptophyl-alanine Methyl Ester

Product 1

HCID 178462140Nalpha-Benzyloxycarbonyl-histidyl-D-tryptophyl-alanine

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

Under an argon atmosphere, the viscous oil containing tripeptide 20 (ca. 0.253 mol), was hydrolyzed in a solution of MeOH (1500 mL), H20 (500 mL) and NaOH (0.08 g/mL, 11.11 g, 0.278 mol). The reaction was allowed to react at room temperature (ca. 25° C.) while being monitored by HPLC. After two days, HPLC analysis indicated that hydrolysis was complete. The solution was concentrated to a residue in vacuo. Water (500 mL) was then added to the residue. The pH of the resulting solution was ca. 10. This aqueous solution was then extracted with EtOAc (2×500 mL). After this extraction the pH of the aqueous layer was ca. 9. All insoluble material in the aqueous layer was collected by vacuum filtration. The pH of the filtrate was then adjusted to ca. 5 with 2N HCl. This resulted in the precipitation of an oil which was isolated from the aqueous layer by decantation. The oil was taken up in a methanol-water solution and concentrated to a residue in vacuo (109.42 g, 0.200 mol, ca. 79% overall yield from dipeptide 26). This isolated material was consistent with 27 by 1H NMR FDMS=547, M+1.

Workup

  1. customto react at room temperature (ca. 25° C.)
  2. customHPLC analysis indicated that hydrolysis
  3. concentrationThe solution was concentrated to a residue in vacuo
  4. additionWater (500 mL) was then added to the residue
  5. extractionThis aqueous solution was then extracted with EtOAc (2×500 mL)
  6. extractionAfter this extraction the pH of the aqueous layer
  7. filtrationAll insoluble material in the aqueous layer was collected by vacuum filtration
  8. customThis resulted in the precipitation of an oil which
  9. customwas isolated from the aqueous layer by decantation
  10. concentrationconcentrated to a residue in vacuo (109.42 g, 0.200 mol, ca. 79% overall yield from dipeptide 26)

Sources & evidence

ORD record
ord-03d6373184ca4d98a707229aefb6e8f8
Source dataset
uspto-grants-1994_06
Patent number
US05322931

Reaction notes

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