Water → HCID 54533981, compound

HRID 1482161Notes

Reaction equation

HRID 1482161 reaction equation
[NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].[NH:10]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@H:11]([C:16](ON1C(=O)CCC1=O)=[O:17])[C@H:12]([CH2:14][CH3:15])[CH3:13].OS([O-])(=O)=O.[K+].O>C(OC(C)C)(=O)C.[Na+].[Cl-]>[NH:10]([C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])[C@H:11]([C:16]([NH:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5])=[O:17])[C@H:12]([CH2:14][CH3:15])[CH3:13]

Participants

7

Reactant 4

HCID 962WaterHCID 6106L-Leucine2×HCID 333451Boc-Ile-OSuHCID 516920Potassium bisulfate

Product 1

HCID 54533981HCID 54533981, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 5234Sodium ChlorideSolvent2×HCID 7915Isopropyl AcetateSolvent

Procedure

1.01 equivalents of H-Leu-OH (Mw=131.2) was first silylated with 2.10 equivalents TMA (Mw=145.12) at about 50° C. until a clear solution was obtained. The solution was cooled to room temperature and diluted with isopropyl acetate. 1.00 equivalent of the Boc-Ile-OSu solid (Mw=328.26; 100.0%) was then added to silylated H-Leu-OH solution. The reaction mixture was further stirred at room temperature for at least 8 hours. After the completion of the reaction was confirmed by HPLC, the solution was quenched by adding DMAPA and water, washed with KHSO4 (1.00 equivalent) in 500 ml 5% (weight) aqueous NaCl solution; 500 ml 5% (weight) aqueous NaCl solution, and water. After evaporation of the isopropyl acetate in vacuo, the excess of water was eliminated by azeotropic distillation with isopropyl acetate. The peptide precipitated during the concentration. The concentrated suspension was then diluted in cyclohexane. The precipitate was stirred at room temperature for at least 10 min, filtered and finally dried in vacuum at 45° C. The dried precipitate yielded (based on NMR content) 80% of Boc-Ile-Leu-OH as white solid.

Workup

  1. customwas first silylated with 2.10 equivalents TMA (Mw=145.12) at about 50° C. until a clear solution
  2. customwas obtained
  3. customthe solution was quenched
  4. additionby adding DMAPA and water
  5. customAfter evaporation of the isopropyl acetate in vacuo
  6. distillationthe excess of water was eliminated by azeotropic distillation with isopropyl acetate
  7. customThe peptide precipitated during the concentration
  8. additionThe concentrated suspension was then diluted in cyclohexane
  9. stirringThe precipitate was stirred at room temperature for at least 10 min
  10. filtrationfiltered
  11. customfinally dried in vacuum at 45° C

Sources & evidence

ORD record
ord-92b52ee179d84f77ac859962bb5b1206
Source dataset
uspto-grants-2016_08
Patent number
US09409946B2

Reaction notes

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