Sodium Hydroxide → N,N'-Bis(1,3-dihydroxy-2-propyl)-5-[N-(2-hydroxy-3-methoxypropyl)acetamido]-2,4,6-triiodoisophthalamide

HRID 1590529

Reaction equation

HRID 1590529 reaction equation
[C:1]([NH:4][C:5]1[C:6]([I:29])=[C:7]([C:21]([NH:23][CH:24]([CH2:27][OH:28])[CH2:25][OH:26])=[O:22])[C:8]([I:20])=[C:9]([C:18]=1[I:19])[C:10]([NH:12][CH:13]([CH2:16][OH:17])[CH2:14][OH:15])=[O:11])(=[O:3])[CH3:2].[OH-].[Na+].[OH:32][CH:33]([CH2:36][O:37][CH3:38])[CH2:34]Cl>C(O)C(O)C.CO>[OH:26][CH2:25][CH:24]([NH:23][C:21](=[O:22])[C:7]1[C:6]([I:29])=[C:5]([N:4]([CH2:34][CH:33]([OH:32])[CH2:36][O:37][CH3:38])[C:1](=[O:3])[CH3:2])[C:18]([I:19])=[C:9]([C:10]([NH:12][CH:13]([CH2:16][OH:17])[CH2:14][OH:15])=[O:11])[C:8]=1[I:20])[CH2:27][OH:28]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 979881-Chloro-3-methoxypropan-2-olHCID 13140687Iopamidol ep impurity C

Product 1

HCID 53648613N,N'-Bis(1,3-dihydroxy-2-propyl)-5-[N-(2-hydroxy-3-methoxypropyl)acetamido]-2,4,6-triiodoisophthalamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1030Propylene GlycolSolvent

Procedure

5-Acetamido-N,N'-bis(1,3-dihydroxy-2-propyl)-2,4,6-triiodoisophthalamide (1036 g, 1.39 mol) was slurried in a mixture of propylene glycol (4170 ml) and methanol (4170 ml). After adding 18.25 M sodium hydroxide (114 ml, 2.08 mol), the mixture was heated at about 50°. When all or nearly all of the starting material was dissolved, the excess of methanol was evaporated in vacuo. Thereafter 2-hydroxy-3-methoxypropyl chloride (259 g, 2.08 mol) was added. The reaction mixture was heated at 50° for 44 hours and then stored at room temperature for 44 hours. Ater neutralization with concentrated hydrochloric acid, the reaction mixture was evaporated in vacuo. The residue was dissolved in methanol (3500 ml) and treated with a mixture of Dowex anion exchange resin 1×4 (2.87 kg) and Amberlite cation exchange resin (1.2 kg). The ion exchange resin was filtered off and washed with 80% aqueous methanol. The filtrate was evaporated in vacuo to dryness and the residue dissolved in isopropyl alcohol (5 1) at 80°. The product was precipitated by cooling to 13.5° and collected on a filter. Further purification was performed by recrystallization from isopropyl alcohol (4 1).

Workup

  1. temperaturethe mixture was heated at about 50°
  2. dissolutionWhen all or nearly all of the starting material was dissolved
  3. customthe excess of methanol was evaporated in vacuo
  4. temperatureThe reaction mixture was heated at 50° for 44 hours
  5. customAter neutralization with concentrated hydrochloric acid, the reaction mixture was evaporated in vacuo
  6. dissolutionThe residue was dissolved in methanol (3500 ml)
  7. additiontreated with a mixture of Dowex anion exchange resin 1×4 (2.87 kg) and Amberlite cation exchange resin (1.2 kg)
  8. filtrationThe ion exchange resin was filtered off
  9. washwashed with 80% aqueous methanol
  10. customThe filtrate was evaporated in vacuo to dryness
  11. dissolutionthe residue dissolved in isopropyl alcohol (5 1) at 80°
  12. customThe product was precipitated
  13. temperatureby cooling to 13.5°
  14. customcollected on a filter
  15. customFurther purification
  16. customwas performed by recrystallization from isopropyl alcohol (4 1)

Sources & evidence

ORD record
ord-f136ea4f0f6f43ea95ebb35458421e74
Source dataset
uspto-grants-1993_04
Patent number
US05204086

Linked notes

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