Process for iohexol manufacture

1 . A process for the production of iohexol comprising alkylating 5-(acetamido)-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophtalamide with a 2,3-dihydroxypropylating agent in the presence of a base and of a solvent which solvent comprises a C 1 -C 5 -monoalkylether of a C 3 -C 10 alkylene-glycol.

2 . A process as claimed in claim 1 wherein said glycol is 1-methoxy-2-propanol.

3 . A process as claimed in claim 1 further comprising one or more co-solvents.

4 . A process as claimed in claim 3 wherein said co-solvents comprise C 1 -C 4 alkanols, preferably methanol, and/or water.

5 . A process as claimed in claim 3 on wherein said solvent comprises 1-methoxy-2-propanol and 0-40 volume % of methanol.

6 . A process as claimed in claim 3 on wherein said solvent comprises 1-methoxy-2-propanol and 0-20 volume % of water.

7 . A process as claimed in claim 1 wherein said solvent is used in an amount of 0.5 to 5 ml, more preferred 0.7 to 3 ml and most preferred 0.9 to 1.0 ml per gram 5-Acetamide.

8 . A process as claimed in claim 1 further comprising purifying the crude iohexol obtained from the N-alkylation reaction using a solvent comprising a C 1 -C 5 -monoalkylether of a C 3 -C 10 alkylene-glycol.

9 . A process as claimed in claim 8 wherein the C 1 -C 5 -monoalkylether of a C 3 -C 10 alkylene-glycol is the same glycol as used in the N-alkylation process.

10 . A process as claimed in claim 8 wherein in said purification the C 1 -C 5 -monoalkylether of a C 3 -C 10 alkylene-glycol is 1-methoxy-2-propanol.

11 . A process as claimed in claim 8 wherein said purification the solvent further comprises one or more co-solvents.

12 . A process as claimed in claim 11 wherein said co-solvent comprises C 1 -C 4 alkanols and preferably methanol.

13 . A process as claimed in claim 9 wherein the amount of said solvent is adjusted to 1.5 to 8 ml of the C 1 -C 5 -monoalkylether of a C 3 -C 10 alkylene-glycol/g iohexol, to 0-1 ml C 1 -C 4 alkanol/g iohexol, and to 0.001-0.3 ml water/g iohexol.

14 . A process as claimed in claim 8 wherein the purification is performed by crystallising the iohexol from said solvent and then separating the crystals from said solvent.

15 . A process as claimed in claim 8 wherein the salt content in the reaction mixture of the alkylation reaction is reduced prior to the purification step.

16 . A process as claimed in claim 8 wherein the water content in the reaction mixture of the alkylation reaction is reduced prior to the crystallisation step preferably by azeotropic distillation.

17 . A process as claimed in claim 8 wherein the crystalline iohexol is washed with isopropanol and dried.