Sodium Hydroxide → Boc-Pro-His-OH

HRID 1982302Notes

Reaction equation

HRID 1982302 reaction equation
[N:1]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14][CH2:13][C@H:2]1[C:3]([O:5]N1C(=O)CCC1=O)=O.[NH2:23][C@H:24]([C:31]([OH:33])=[O:32])[CH2:25][C:26]1[N:30]=[CH:29][NH:28][CH:27]=1.[OH-].[Na+]>O.O1CCOCC1>[N:1]1([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:15][CH2:14][CH2:13][C@H:2]1[C:3]([NH:23][C@H:24]([C:31]([OH:33])=[O:32])[CH2:25][C:26]1[N:30]=[CH:29][NH:28][CH:27]=1)=[O:5]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 8538831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) 2-(2,5-dioxo-1-pyrrolidinyl) ester, (2S)-HCID 178419078HCID 178419078, compound

Product 1

HCID 178451947Boc-Pro-His-OH

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

1.25 g of Boc-Pro-OSu [G. W. Anderson et al., J. Amer. Chem. Soc. 86, 1839 (1964)] and 0.68 g of H-His-OH are suspended in 4 ml of H2O and 2 ml of dioxan. While stirring vigorously, 2N NaOH is added by means of a pH stat at a pH value of 9.0. After 45 minutes the absorption of NaOH ceases. The now clear solution is stirred for a further 10 minutes, the pH value is adjusted subsequently to 5.0 with 4N HCl, and the whole is concentrated to approximately 5 ml. After the addition of 20 ml of H2O, the whole is again concentrated to approximately 5 ml and then purified by chromatography over a column of absorber resin, diaion HP-20 (φ=1.6 cm; length=20 cm). The bulk of this product is eluted with 20% isopropanol in H2O. The fractions that are pure according to thin layer chromatography are combined, concentrated almost to dryness and, after the addition of H2O, lyophilised, yielding Boc-Pro-His-OH in the form of an amorphous powder; Rf (E)=0.45; Rf (A)=0.21.

Workup

  1. customAfter 45 minutes the absorption of NaOH ceases
  2. stirringThe now clear solution is stirred for a further 10 minutes
  3. concentrationthe whole is concentrated to approximately 5 ml
  4. additionAfter the addition of 20 ml of H2O
  5. concentrationthe whole is again concentrated to approximately 5 ml
  6. custompurified by chromatography over a column of absorber resin, diaion HP-20 (φ=1.6 cm; length=20 cm)
  7. washThe bulk of this product is eluted with 20% isopropanol in H2O
  8. concentrationconcentrated almost to dryness
  9. additionafter the addition of H2O

Sources & evidence

ORD record
ord-e4dcdf7b8eec43119defa4c35359598b
Source dataset
uspto-grants-1986_06
Patent number
US04595677

Reaction notes

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