Lithium complexes of N-(1-hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane, their production and use
View Patent ↗The invention relates to crystalline lithium complexes of N-(1-hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10 tetraazacyclododecane, their production and the recovery of the salt-free gadolinium complex of N-(1-hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10 tetraazacyclododecane from the latter without the use of ion exchangers.
1. A compound of formula I
in which the three X's altogether, independently, stand for n lithium ions and m hydrogen atoms, whereby n and m in each case, independently, mean the numbers 0 to 3, and the sum of n and m=3, and Y has the meaning of chloride or bromide.
2. A process for production of a compound of formula I according to claim 1 , comprising reacting N-(6-hydroxy-2,2-dimethyl-1,3-dioxepan-5-yl)-1,4,7,10-tetraazacyclododecane or its complex with lithium chloride or lithium bromide with chloroacetic acid or bromoacetic acid and lithium hydroxide in polar solvent at a temperature of 40-150° C. and a pH of 8-14.
3. A method of producing a compound of formula II
comprising complexing a compound of formula I according to claim 1 .
4. A compound of formula I according to claim 1 , wherein Y stands for chloride, and one X stands for a lithium ion, and the two remaining X's stand for hydrogen atoms.
5. A compound of formula I according to claim 1 , wherein n and m in each case independently mean the numbers 0.8-2.2.
6. A compound of formula I according to claim 1 , wherein the compound is in crystalline form.
7. A process according to claim 2 , further comprising crystallizing a compound of formula I according to claim 1 from an ethanol-water mixture.
8. A method according to claim 3 , further comprising isolating salt-free a compound of formula II from ethanol/water without using an ion exchanger.
9. A process according to claim 2 , further comprising recovering lithium hydroxide by treatment with an anion exchanger.
10. A process according to claim 2 , wherein the polar solvent is water, a primary alcohol, a secondary alcohol, DMF, dimethoxy-ethane, diethylene glycol dimethyl ether, or a mixture thereof.
11. A process according to claim 2 , wherein the polar solvent is ethanol or isopropanol.
12. A process according to claim 2 , wherein the reaction is at a temperature of 40°-90° C.
13. A process according to claim 2 , wherein the pH is within the range of 9-13.
14. A process according to claim 2 , wherein the reaction is carried out for 0.5-24 hours.
15. A process according to claim 2 , wherein the reaction is carried out for 1-6 hours.
16. A process according to claim 2 , further comprising isolating the compound of formula I by setting the pH within the range of 3.5-4.5 with hydrochloric acid, hydrobromic acid, acetic acid, trifluoroacetic acid, or p-toluene sulfonic acid.
17. A process according to claim 2 , further comprising isolating the compound by setting the pH within the range of 3.8-4.2.
18. A process according to claim 17 , wherein the pH is set with hydrochloric acid.
19. A method according to claim 3 , further comprising dissolving a compound of formula I in water, setting a pH of about 3.6 by adding hydrochloric acid, adding a calculated amount of gadolinium oxide, complexing at 50-100° C., and crystallizing the compound of formula II by adding ethanol.