Ammonia → Rufinamide

HRID 1927189Notes

Reaction equation

HRID 1927189 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[CH2:4]Br.[N-:11]=[N+:12]=[N-:13].[Na+].[N-]=[N+]=[N-].[C:18]([O:22]C)(=O)[C:19]#[CH:20].[NH3:24]>O>[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[CH2:4][N:11]1[CH:20]=[C:19]([C:18]([NH2:24])=[O:22])[N:13]=[N:12]1

Participants

7

Reactant 5

HCID 222AmmoniaHCID 13536Methyl propiolateHCID 33557Sodium AzideHCID 33558AzideHCID 5814352-(Bromomethyl)-1,3-difluorobenzene

Product 1

HCID 129228Rufinamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In a 250 ml round bottom flask, 2,6-difluorobenzylbromide (0.024 mol, 5 g), sodium azide (0.026 mol, 1.72 g) and water (50 ml) were added. The reaction mixture was heated to 70° C. to 75° C. for 30 hours and formation of the azide intermediate was monitored by thin layer chromatography (TLC). After the completion of reaction, the reaction contents were cooled to room temperature and then to this methyl propiolate (0.024 mol, 2.1 ml) was added dropwise, maintaining the contents at room temperature. On complete addition, the mixture was again heated at 60° C. to 65° C. for 4 to 5 hours. After the reaction was completed, the contents were cooled to room temperature and to this 25% aqueous ammonia (40 ml) solution was added dropwise. The reaction contents were heated to 70° C. to 75° C. for 4 to 5 hours and then gradually cooled to room temperature. The solid obtained was filtered and washed with water. The product was dried under vacuum at 70° C.-75° C. to give 3.0 g of rufinamide.

Workup

  1. temperatureThe reaction mixture was heated to 70° C. to 75° C. for 30 hours
  2. customAfter the completion of reaction
  3. customthe reaction contents
  4. temperaturemaintaining the contents at room temperature
  5. additionOn complete addition
  6. temperaturethe mixture was again heated at 60° C. to 65° C. for 4 to 5 hours
  7. additionwas added dropwise
  8. customThe reaction contents
  9. temperaturewere heated to 70° C. to 75° C. for 4 to 5 hours
  10. temperaturegradually cooled to room temperature
  11. customThe solid obtained
  12. filtrationwas filtered
  13. washwashed with water
  14. customThe product was dried under vacuum at 70° C.-75° C.

Sources & evidence

ORD record
ord-3b66de5870c94bd2b0ca55ae65111a45
Source dataset
uspto-grants-2012_05
Patent number
US08183269B2

Reaction notes

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