Triethylamine → Phenytoin Impurity 31

HRID 1768323Notes

Reaction equation

HRID 1768323 reaction equation
[OH:1][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].C(N(CC)CC)C.CS(Cl)(=O)=O.[P:34]([O-])([O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35]>O1CCCC1>[CH2:45]([O:44][P:34](=[O:35])([O:36][CH2:37][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[O:1][CH2:2][N:3]1[C:7](=[O:8])[C:6]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[NH:5][C:4]1=[O:21])[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 1613663-(Hydroxymethyl)phenytoinHCID 4193600Dibenzylphosphate

Product 1

HCID 11984247Phenytoin Impurity 31

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

5.0 g (17.7 mmol) of 3-(hydroxymethyl)-5,5-diphenylimidazolidine-2,4-dione (hydroxymethylphenytoin) and 7.5 g (74.1 mmol) of triethylamine were dissolved in 30 g of tetrahydrofuran (THF). A solution of 2.4 g (21.0 mmol) of methanesulfonyl chloride in 33.3 g of THF was added at −10 to −5° C. A white suspension formed. The suspension was filtered and the clear filtrate was added to a suspension of 5.8 g (20.8 mmol) of dibenzyl phosphate in 5.0 g of THF at room temperature. After stirring overnight, the mixture was concentrated on a rotary evaporator, 50 g of ethyl acetate and 25 g of water were then added to the residue and the phases were separated. The organic phase was washed once with 20 g of water and then extensively concentrated on a rotary evaporator. 2.5 g of acetone and seed material were added to the residue obtained and the mixture was stirred overnight at 0 to 10° C. The resulting colourless precipitate was filtered off and dried under vacuum. Yield: 6.9 g (72%).

Workup

  1. customA white suspension formed
  2. filtrationThe suspension was filtered
  3. concentrationthe mixture was concentrated on a rotary evaporator, 50 g of ethyl acetate and 25 g of water
  4. additionwere then added to the residue
  5. customthe phases were separated
  6. washThe organic phase was washed once with 20 g of water
  7. concentrationextensively concentrated on a rotary evaporator
  8. addition2.5 g of acetone and seed material were added to the residue
  9. customobtained
  10. stirringthe mixture was stirred overnight at 0 to 10° C
  11. filtrationThe resulting colourless precipitate was filtered off
  12. customdried under vacuum

Sources & evidence

ORD record
ord-5e99c7de2a8b40ba98c821c0cca8ef14
Source dataset
uspto-grants-2007_06
Patent number
US07235666B2

Reaction notes

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