Boric Acid → 5,5'-(2,7-dihydroxyoctane-1,8-diyl)bis(acetylazanediyl)bis(N1,N1,N3, N3-tetrakis(2-hydroxyethyl)-2,4,6-triiodoisophthalamide)

HRID 41828

Reaction equation

HRID 41828 reaction equation
[C:1]([NH:4][C:5]1[C:6]([I:31])=[C:7]([C:22]([N:24]([CH2:28][CH2:29][OH:30])[CH2:25][CH2:26][OH:27])=[O:23])[C:8]([I:21])=[C:9]([C:19]=1[I:20])[C:10]([N:12]([CH2:16][CH2:17][OH:18])[CH2:13][CH2:14][OH:15])=[O:11])(=[O:3])[CH3:2].[OH-:32].[K+].B(O)(O)O.[O:38]1[CH2:40][CH:39]1[CH2:41][CH2:42][CH2:43][CH2:44][CH:45]1[CH2:47][O:46]1>CO.O>[OH:38][CH:39]([CH2:41][CH2:42][CH2:43][CH2:44][CH:45]([OH:46])[CH2:47][N:4]([C:5]1[C:19]([I:20])=[C:9]([C:10]([N:12]([CH2:13][CH2:14][OH:15])[CH2:16][CH2:17][OH:18])=[O:11])[C:8]([I:21])=[C:7]([C:6]=1[I:31])[C:22]([N:24]([CH2:25][CH2:26][OH:27])[CH2:28][CH2:29][OH:30])=[O:23])[C:1](=[O:32])[CH3:2])[CH2:40][N:4]([C:5]1[C:19]([I:20])=[C:9]([C:10]([N:12]([CH2:13][CH2:14][OH:15])[CH2:16][CH2:17][OH:18])=[O:11])[C:8]([I:21])=[C:7]([C:6]=1[I:31])[C:22]([N:24]([CH2:25][CH2:26][OH:27])[CH2:28][CH2:29][OH:30])=[O:23])[C:1](=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 7628Boric Acid2×HCID 14797Potassium Hydroxide2×HCID 170481,2:7,8-DiepoxyoctaneHCID 131423805-Acetylamino-N,N,N',N'-tetrakis-(2-hydroxy-ethyl)-2,4,6-triiodo-isophthalamide

Product 1

HCID 442187915,5'-(2,7-dihydroxyoctane-1,8-diyl)bis(acetylazanediyl)bis(N1,N1,N3, N3-tetrakis(2-hydroxyethyl)-2,4,6-triiodoisophthalamide)

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

5-Acetylamino-N,N,N′,N′-tetrakis-(2-hydroxy-ethyl)-2,4,6-triiodo-isophthalamide (5 g, 6.45 mmol) was added to a stirring solution of potassium hydroxide (0.54 g, 6.5 mmol) in a mixture of methanol (3.5 ml) and water (3.5 ml). To the clear and slightly yellow solution which was obtained was added boric acid (0.35 g, 5.6 mmol). The pH was continuously maintained at pH 12.6 by addition of potassium hydroxide (10 M) and then 2-(4-oxiran-2-ylbutyl)oxirane (0.32 g, 2.24 mmol) was added. The pH of the solution was continuously maintained within the interval 12 and 13 by addition of solid boric acid for 5 hours. And the mixture stirred at ambient temperature overnight (20 hours). LC-MS investigation showed formation of the expected product. Using 18.5 M HCl (50%), the mixture was made acidic, pH 3.5-4.5 and stirred overnight again. Precipitation of unreacted monomer had occurred and removed by filtration of the mixture (funnel sinter 3) and the filter cake washed with water (2×5 ml). The filtrate was then treated with ion exchangers (AMB200C, 9 ml) and (IRA-67, 10 ml). The resins were removed by filtration and rinsed with water and the combined aqueous volume was reduced in vacuo. The crude product was purified by preparative HPLC (column Phenomenex Luna C18 (2) 10 μm 250×50.0 mm, solvents: A=water and B=acetonitrile; gradient 0-10% B over 60 min; flow 50.0 ml/min, UV detection at 214 nm and 254 nm). After freeze-drying, 869 mg of the title product (47%) was obtained.

Workup

  1. customTo the clear and slightly yellow solution which was obtained

Sources & evidence

ORD record
ord-8d6fbfb805084fae85c28a2dd5b12ad7
Source dataset
uspto-grants-2013_09
Patent number
US08535642B2

Linked notes

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