Potassium Iodide → Phenytoin Impurity 31

HRID 377023

Reaction equation

HRID 377023 reaction equation
Cl[CH2:2][N:3]1[C:7](=[O:8])[C:6]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[NH:5][C:4]1=[O:21].[P:22]([O-:40])([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23].[K+].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C>[O:21]=[C:4]1[NH:5][C:6]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:7](=[O:8])[N:3]1[CH2:2][O:40][P:22](=[O:23])([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 110986333-(Chloromethyl)-5,5-diphenylimidazolidine-2,4-dioneHCID 23666573Potassium dibenzyl phosphate

Product 1

HCID 11984247Phenytoin Impurity 31Yield 70%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 250 kg 3-(chloromethyl)-5,5-diphenyl-2,4-imidazolidinedione from Step (A), 270 kg of potassium dibenzyl phosphate, 6 kg of potassium carbonate, 0.75 kg of potassium iodide, and 500 kg of acetonitrile is heated at 70° C. to reflux for 2 to 5 hours or until the reaction is essentially complete. The reaction mixture is cooled to 40° C. to 65° C. and filtered. The solution is stirred with at least 11 kg of activated carbon and filtered using a filter-aid. The reaction solvent is replaced by adding toluene in portions and vacuum distilling. The resulting slurry is cooled to less than 5° C. The title compound is collected by filtration and washed with cold toluene. The wet cake is dried at 50° C. under vacuum to give phosphoric acid dibenzyl ester 2,5-dioxo-4,4-diphenyl-imidazolidin-1-ylmethyl ester, 315 kg (70% yield); mp 118.6-119.7° C.

Workup

  1. temperatureto reflux for 2 to 5 hours or until the reaction
  2. temperatureThe reaction mixture is cooled to 40° C. to 65° C.
  3. filtrationfiltered
  4. filtrationfiltered
  5. additionby adding toluene in portions and vacuum
  6. distillationdistilling
  7. temperatureThe resulting slurry is cooled to less than 5° C
  8. filtrationThe title compound is collected by filtration
  9. washwashed with cold toluene
  10. customThe wet cake is dried at 50° C. under vacuum

Sources & evidence

ORD record
ord-1292fcfd5af64490afc162f787b32ca3
Source dataset
uspto-grants-2000_02
Patent number
US06022975

Linked notes

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