Sodium Carbonate → 3-Amino-2,4,6-triiodo-5-(methylcarbamoyl)benzoyl chloride

The flask was charged with thionyl chloride (600 ml, 978.6 g, 8.23 mol) and 5-amino-3-methylcarbamoyl-2,4,6-triiodobenzoic acid (320 g, 0.56 mol) was added in portions with stirring. The mixture was refluxed for one hour and an additional 100 ml of thionyl chloride was added. Refluxing was continued for 1.5 hours (total reflux time: 2.5 hours) until TLC indicated that the reaction was complete. Thionyl chloride was removed by vacuum distillation (30° C., 75 mmHg) until the consistency of the residue was pasty. The remaining traces of thionyl chloride were removed by three consecutive vacuum codistillations with 200 ml of THF. The resulting yellow paste was dissolved in 600 ml of THF and immersed in an ice bath while 500 ml of saturated NaCl was added. The pH of the aqueous layer (<1) was adjusted to approximately 6.9 with solid sodium carbonate (173 g, 1.63 mol) The mixture was filtered and the filter cake was washed with 200 ml of THF. The wash was combined with the mother liquor which was then allowed to separate into two layers. The organic layer was washed with 200 ml of saturated NaCl, the aqueous layer with 150 ml THF: the organic layers were combined and dried over 180 g of calcium chloride beads for one hour. The solution was concentrated to a volume of 400 ml and stirred with 200 ml of dry toluene for 16 hours. The creamy white solid thus formed was filtered, washed with 2×100 ml of dry cold toluene and dried under vacuum to give 228 g of product 2 (0.39 mol, 69%) as a pale yellow solid. 13C NMR (75.5 MHz, DMSO, ref. DMSO at 39.5 ppm): 170.2, 150.4, 148.9, 148.7, 83.0, 75.3, 70.1, 25.8. TLC: One spot (EtOAc/MeOH/HOAc, 10/5/1).

1. additionwas added in portions
2. temperatureThe mixture was refluxed for one hour
3. temperatureRefluxing
4. custom(total reflux time: 2.5 hours)
5. customThionyl chloride was removed by vacuum distillation (30° C., 75 mmHg) until the consistency of the residue
6. customThe remaining traces of thionyl chloride were removed by three consecutive vacuum codistillations with 200 ml of THF
7. dissolutionThe resulting yellow paste was dissolved in 600 ml of THF
8. customimmersed in an ice bath while 500 ml of saturated NaCl
9. additionwas added
10. filtrationwas filtered
11. washthe filter cake was washed with 200 ml of THF
12. customto separate into two layers
13. washThe organic layer was washed with 200 ml of saturated NaCl
14. dry with materialdried over 180 g of calcium chloride
15. waitbeads for one hour
16. concentrationThe solution was concentrated to a volume of 400 ml
17. stirringstirred with 200 ml of dry toluene for 16 hours
18. customThe creamy white solid thus formed
19. filtrationwas filtered
20. washwashed with 2×100 ml of dry cold toluene
21. customdried under vacuum

ORD record

ord-e344bda109c341b798904619ca64dec8

Source dataset

uspto-grants-1991_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05019371