Acetic Acid → HCID 178454187, compound

HRID 1731589Notes

Reaction equation

HRID 1731589 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.CC(O)=O>CN(C=O)C.CO.CCCCO>[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

8

Reactant 4

HCID 176Acetic AcidHCID 62365Isobutyl chloroformateHCID 201587Mesalamine hydrochlorideHCID 178454195HCID 178454195, compound

Product 1

HCID 178454187HCID 178454187, compoundYield 146.1%

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

381.1 Grams (1.16 mol) of BOC-Arg-OH.HCl.H2O was dissolved in 1,392 ml of DMF, and then 151 ml of NEM was added thereto, followed by dropwise addition of 152.3 ml of isobutyl chloroformate at -20° C. After 10 minutes reaction, a 928 ml DMF solution of 219.8 g (1.16 mol) of 5-aminosalicylic acid hydrochloride and 301.6 ml of NEM was added dropwise to said reaction mixture at -15° to -10° C. The reaction was continued for 3 hours at the same temperature and additionally continued for 15 hours at room temperature. After the reaction was completed, the DMF was removed by evaporation under a reduced pressure and the residue obtained was dissolved in 464 ml of MeOH and 332 ml of n-BuOH. To the mixture was added with 3,300 ml of AcOH, washed twice with 2,160 ml of cold 5% hydrochloric acid saturated with sodium chloride, then dried with anhydrous magnesium sulfate. After drying, the magnesium sulfate was removed by filtration and the solvent was removed by evaporation under a reduced pressure to obtain 464.8 g (89.9%) of BOC-Arg-CHA.HCl. Rf1 =0.64. Melting point: 225.0° C. (decomposed). [α]D20 -10.7 (C=1, MeOH).

Workup

  1. addition151 ml of NEM was added
  2. customAfter 10 minutes reaction
  3. customreaction mixture at -15° to -10° C
  4. waitadditionally continued for 15 hours at room temperature
  5. customthe DMF was removed by evaporation under a reduced pressure
  6. customthe residue obtained
  7. washwashed twice with 2,160 ml of cold 5% hydrochloric acid saturated with sodium chloride
  8. dry with materialdried with anhydrous magnesium sulfate
  9. customAfter drying
  10. customthe magnesium sulfate was removed by filtration
  11. customthe solvent was removed by evaporation under a reduced pressure

Sources & evidence

ORD record
ord-751a2c342b294b98a7c59fa293dc1afc
Source dataset
uspto-grants-1986_11
Patent number
US04622389

Reaction notes

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