Reaction #1375816

Reaction equation

glycidyl-tert-butyl ether

1,4,7-tris-carboxymethyl-1,4,7,10-tetraazacyclododecane

potassium hydroxide

→

10-(2-Hydroxy-3-tert-butyloxy-propyl)-1,4,7-tris-carboxymethyl-1,4,7,10-tetraazacyclododecane

Solvents

dioxane

water

Conditions

Workup

1. 1
   OtherIt is evaporated to dryness
2. 2
   Extractionextracted twice with 100 ml of tert-butyl-methyl ether
3. 3
   Otherevaporated to dryness
4. 4
   Extraction(extracted) with 200 ml of methanol/80 ml of methylene chloride
5. 5
   TemperatureIt is cooled in an ice bath
6. 6
   Otherprecipitated potassium chloride
7. 7
   Filtrationis filtered out
8. 8
   ConcentrationThe filtrate is concentrated by evaporation in a vacuum
9. 9
   workup.DISSOLUTIONthe residue is dissolved in 45 ml of water/20 ml of ethanol
10. 10
    WashThe product is eluted with a solution of ethanol/water 1:3
11. 11
    ConcentrationAfter concentration
12. 12
    Otherby evaporation in a vacuum
13. 13
    Otherthe residue is chromatographed on a reversed-phase column (RP 18/mobile solvent =gradient of water/tetrahydrofuran)
14. 14
    ConcentrationAfter concentration
15. 15
    Otherby evaporation of the main fraction, 10.38 g (71% of theory) of a strongly hygroscopic, vitreous solid
16. 16
    Otheris obtained

Procedure

11.27 g (86.58 mmol) of glycidyl-tert-butyl ether and 10 g (28.86 mmol) of 1,4,7-tris-carboxymethyl-1,4,7,10-tetraazacyclododecane are dissolved in a mixture of 50 ml of dioxane/80 ml of water, and the pH is brought to 10 with 6 N potassium hydroxide solution. It is stirred for 24 hours at 70° C. It is evaporated to dryness, the residue is taken up with 300 ml of water/50 ml of methanol and extracted twice with 100 ml of tert-butyl-methyl ether. The aqueous solution is adjusted to pH 1 with 5 N hydrochloric acid and evaporated to dryness. The residue is boiled out (extracted) with 200 ml of methanol/80 ml of methylene chloride. It is cooled in an ice bath and precipitated potassium chloride is filtered out. The filtrate is concentrated by evaporation in a vacuum, the residue is dissolved in 45 ml of water/20 ml of ethanol and then put on a column of poly-(4-vinylpyridine). The product is eluted with a solution of ethanol/water 1:3. After concentration by evaporation in a vacuum, the residue is chromatographed on a reversed-phase column (RP 18/mobile solvent =gradient of water/tetrahydrofuran). After concentration by evaporation of the main fraction, 10.38 g (71% of theory) of a strongly hygroscopic, vitreous solid is obtained.

Source