Water → HCID 178523874, compound

HRID 1109818Notes

Reaction equation

HRID 1109818 reaction equation
[OH-].[Na+].C[O:4][C:5](=[O:38])[C@@H:6]([CH2:28][C:29]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[NH:31][CH:30]=1)[NH:7][C:8](=[O:27])[C@H:9]([CH2:21][C:22]1[N:26]=[CH:25][NH:24][CH:23]=1)[NH:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12].O>CO>[CH2:14]([O:13][C:11]([NH:10][C@H:9]([C:8]([NH:7][C@@H:6]([C:5]([OH:38])=[O:4])[CH2:28][C:29]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[NH:31][CH:30]=1)=[O:27])[CH2:21][C:22]1[N:26]=[CH:25][NH:24][CH:23]=1)=[O:12])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 178501393HCID 178501393, compound

Product 1

HCID 178523874HCID 178523874, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Aqueous sodium hydroxide (15.4 g, 192 mL, 0.08 g/mL solution, 0.38 mol) was added to a solution of dipeptide 25 (187.1 g, ca. 0.38 mol), water (360 mL) and MeOH (ca. 6 L). The solution was stirred at room temperature until hydrolysis was complete (ca. 24 hours). The disappearance of the starting peptide was established by HPLC analysis. The solution was concentrated in vacuo to a residue which was dissolved in water (ca. 1 L). The aqueous layer (pH ca. 10) was then extracted with EtOAc (2×500 mL) in a separatory funnel. The resulting aqueous phase was adjusted to a pH of 5 with concentrated HCl at which point a crystalline precipitate formed. The solid was collected by vacuum filtration and dried in vacuo (148.4 g, 0.31 mol, 82%). The pH of the filtrate was adjusted to 4.5. A second crop of solid was again collected by vacuum filtration and dried in vacuo (20.2 g, 0.043 mol, 11%). 1H NMR showed both samples to contain dipeptide 26 in high purity. In two repetitions of this reaction, yields of 83% (ca. 0.06 mole scale) and 58% (ca. 0.3 mole scale) were obtained.

Workup

  1. custom(ca. 24 hours)
  2. concentrationThe solution was concentrated in vacuo to a residue which
  3. dissolutionwas dissolved in water (ca. 1 L)
  4. extractionThe aqueous layer (pH ca. 10) was then extracted with EtOAc (2×500 mL) in a separatory funnel
  5. customformed
  6. filtrationThe solid was collected by vacuum filtration
  7. customdried in vacuo (148.4 g, 0.31 mol, 82%)
  8. filtrationA second crop of solid was again collected by vacuum filtration
  9. customdried in vacuo (20.2 g, 0.043 mol, 11%)
  10. customIn two repetitions of this reaction
  11. customyields of 83% (ca. 0.06 mole scale)
  12. custom58% (ca. 0.3 mole scale) were obtained

Sources & evidence

ORD record
ord-ac75bdaec0034c74aa053990efc92749
Source dataset
uspto-grants-1994_06
Patent number
US05322931

Reaction notes

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