Isobutyl chloroformate → HCID 178454187, compound

HRID 1197075Notes

Reaction equation

HRID 1197075 reaction equation
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:9])[NH2:8].Cl.O.ClC(OCC(C)C)=O.Cl.NC1C=C(C(O)=O)C(O)=CC=1>CN(C=O)C>[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:8])[NH2:9]

Participants

5

Reactant 3

HCID 62365Isobutyl chloroformateHCID 201587Mesalamine hydrochlorideHCID 178454195HCID 178454195, compound

Product 1

HCID 178454187HCID 178454187, compoundYield 146.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

After 381.1 g (1.16 mole) of BOC-Arg-OH.HCl.H2O was dissolved in 1392 ml of DMF, 151 ml of NEM was added to the solution. Then, 152.3 ml of isobutyl chloroformate was dropwise added to the solution at -20° C. The resulting mixture was reacted for 10 minutes. After the reaction, 928 ml of a solution of 219.8 g (1.16 mole) of 5-aminosalicylic acid hydrochloride and 301.6 ml of NEM in DMF was dropwise added to the reaction solution at -15° to -10° C. After the dropwise addition, the mixture was reacted at the same temperature for 3 hours and further at room temperature for 15 hours. After the reaction, DMF was removed by distillation under reduced pressure and the residue was dissolved in 464 ml of MeOH and 332 ml of n-BuOH. To the solution was added 3300 ml of AcOEt. After washing twice with 2160 ml of cold 5% hydrochloric acid saturated with sodium chloride, the mixture was dried over anhydrous magnesium sulfate. After drying, magnesium sulfate was filtered off and the solvent was removed by distillation under reduced pressure to give 464.8 g (89.9%) of Boc-Arg-CHA.HCl.

Workup

  1. addition151 ml of NEM was added to the solution
  2. customThe resulting mixture was reacted for 10 minutes
  3. additionwas dropwise added to the reaction solution at -15° to -10° C
  4. additionAfter the dropwise addition
  5. customthe mixture was reacted at the same temperature for 3 hours and further at room temperature for 15 hours
  6. customwas removed by distillation under reduced pressure
  7. dissolutionthe residue was dissolved in 464 ml of MeOH
  8. additionTo the solution was added 3300 ml of AcOEt
  9. washAfter washing twice with 2160 ml of cold 5% hydrochloric acid saturated with sodium chloride
  10. dry with materialthe mixture was dried over anhydrous magnesium sulfate
  11. customAfter drying
  12. filtrationmagnesium sulfate was filtered off
  13. customthe solvent was removed by distillation under reduced pressure

Sources & evidence

ORD record
ord-7741ddd1c0694c68a21125bf5a89c871
Source dataset
uspto-grants-1992_05
Patent number
US05116941

Reaction notes

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