反応 #2307965

反応方程式

NaOH

(S)-2-(Acetyloxy)propanoyl chloride

N,N′-bis[2-acetyloxy-1-[(acetyloxy)methyl]ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide

(S)-2-(acetyloxy)propanoyl chloride

→

Iopamidol

収率 87.0%

溶媒

N,N-dimethylacetamide

反応条件

後処理

1. 1
   その他the temperature of the reaction mixture below 30° C
2. 2
   workup.STIRRINGvigorously stirred at 45° C
3. 3
   濃縮After two hours the mixture is concentrated under vacuum
4. 4
   ろ過After two hours at room temperature the resulting suspension is filtered
5. 5
   洗浄the solid washed with N,N-dimethylacetamide (2×20 mL)
6. 6
   濃縮are concentrated to an oily residue, which
7. 7
   workup.ADDITIONis diluted with water (200 mL)
8. 8
   洗浄is eluted with water
9. 9
   濃縮The eluate is concentrated and loaded onto two ion exchange resin columns (Dowex® C350 15 mL, Relite® MG1 10 mL)
10. 10
    濃縮The eluate is concentrated
11. 11
    その他the solid residue is crystallized from ethanol

実験手順

(S)-2-(Acetyloxy)propanoyl chloride (16.5 g, 110 mmol) is added, over 20 min, to a stirred solution of N,N′-bis[2-acetyloxy-1-[(acetyloxy)methyl]ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide (53.3 g, 61.1 mmol) in N,N-dimethylacetamide (75 mL) while keeping the temperature of the reaction mixture below 30° C. A further amount of (S)-2-(acetyloxy)propanoyl chloride (0.9 g, 6.0 mmol) is added after 24 and 30 hours and the reaction mixture is stirred at the same temperature for additional 15 hours. 5M NaOH (90 mL, 450 mmol) is dripped over a period of 2 hours into the reaction mixture vigorously stirred at 45° C. After two hours the mixture is concentrated under vacuum and reintegrated with additional N,N-dimethylacetamide (200 mL). After two hours at room temperature the resulting suspension is filtered and the solid washed with N,N-dimethylacetamide (2×20 mL). The mother liquors, combined with the washings, are concentrated to an oily residue, which is diluted with water (200 mL) and nanofiltered. The retentate is loaded onto an Amberlite® XAD-16.00 resin column (160 mL) that is eluted with water. The eluate is concentrated and loaded onto two ion exchange resin columns (Dowex® C350 15 mL, Relite® MG1 10 mL). The eluate is concentrated and the solid residue is crystallized from ethanol to afford Iopamidol (41.2 g, 53 mmol).

出典