Reaktion #70112

Reaktionsgleichung

2-{[2-(oxiran-2-ylmethoxy)-ethoxy]methyl}oxirane

potassium hydroxide

5-acetylamino-N,N′-bis-(2,3-dihydroxypropyl)-2,4,6-triiodo-N,N′-dimethyl isophthalamide

HCl

boric acid

→

5,5′-(5,12-dihydroxy-2,15-dioxo-7,10-dioxa-3,14-diazahexadecane-3,14-diyl)bis(N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-N1,N3-dimethylisophthalamide)

Ausbeute 5.0%

Lösungsmittel

acetonitrile

water

water methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITThe reaction was left over weekend
2. 2
   SonstigeSalts were removed by treatment with ion exchanger AMB200C and IRA67
3. 3
   FiltrationThe solution was filtered from the resin
4. 4
   Sonstigeevaporated
5. 5
   SonstigeThe product was purified by preparative HPLC (column YMC amino 21.2×250 mm, solvents
6. 6
   Sonstigeobtained in 180 mg after lyophilisation, 5% yield
7. 7
   workup.WAITgradient 0-30% B over 20 min
8. 8
   Sonstigegave one broad peak centred at 9.6 minutes with m/z 1724.6 (MH+) corresponding to the structure

Vorschrift

To a stirred solution of water/methanol (4.9 ml, 2.5 ml) and potassium hydroxide (0.47 g, 8.4 mmol) at 40° C. was added 5-acetylamino-N,N′-bis-(2,3-dihydroxypropyl)-2,4,6-triiodo-N,N′-dimethyl isophthalamide (5.0 g, 6.5 mmol). To the clear solution was then added boric acid (0.28 g, 4.5 mmol). The mixture was cooled to room temperature and pH adjusted to 12.6. 2-{[2-(oxiran-2-ylmethoxy)-ethoxy]methyl}oxirane (0.382 g, 2.22 mmol) was added. The pH of the solution was adjusted to the interval 12.6-13. The reaction was left over weekend. To the solution was added HCl (18%) to pH 4. Salts were removed by treatment with ion exchanger AMB200C and IRA67. The solution was filtered from the resin and evaporated. The product was purified by preparative HPLC (column YMC amino 21.2×250 mm, solvents: A=water and B=acetonitrile; gradient 85-65% B over 25 min; flow 25.0 ml/min, UV detection at 214 nm and 254 nm), and obtained in 180 mg after lyophilisation, 5% yield. Analysis by LC-MS (column Agilent Zorbax SB-Aq 3.5 μm 3.0×100 mm, solvents: A=water/0.1% formic acid and B=acetonitrile/0.1% formic acid; gradient 0-30% B over 20 min; flow 0.3 ml/min, UV detection at 214 and 254 nm, ESI-MS) gave one broad peak centred at 9.6 minutes with m/z 1724.6 (MH+) corresponding to the structure.

Quelle