Ammonium Chloride → Rufinamide

HRID 335513Notes

Reaction equation

HRID 335513 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:9]=1[CH2:10][N:11]1[CH:15]=[C:14]([C:16](O)=[O:17])[N:13]=[N:12]1.[Cl-].[NH4+:25].C(=O)(O)[O-].[Na+]>C1COCC1>[F:7][C:8]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:9]=1[CH2:10][N:11]1[CH:15]=[C:14]([C:16]([NH2:25])=[O:17])[N:13]=[N:12]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 65578Oxalyl chloride2×HCID 516892Sodium Bicarbonate2×HCID 10014469Cgp-47292

Product 1

HCID 129228RufinamideYield 56.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
22.5 °C

Procedure

3.74 ml (45.65 mmol) of oxalyl chloride were added drop wise to a suspension of 10 g (41.8 mmol) of 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid in ml of anhydrous THF, at 20-25° C. and under nitrogen atmosphere. When the addition of oxalyl chloride was concluded, the mixture was stirred at 20-25° C. for 4 h. Afterwards, the resulting mixture was diluted with 50 ml of anhydrous THF, followed by the distillation of 15 ml at 35-40° C. under vacuum, in order to remove the remaining HCl. The reaction was cooled to 20-25° C. and 8 g (149.57 mmol) of ammonium chloride were added followed by addition of 20 ml of 8% aqueous solution of sodium bicarbonate. After further addition of 8.8 g (104.97 mmol) of sodium bicarbonate, the mixture was left under powerful stirring over 4 h at 20-25° C. To conclude with, the suspension was filtered and washed twice with 50 ml of a saturated aqueous sodium bicarbonate solution and twice with 50 ml of water The solid was dried on a vacuum drier at 50° C. to yield 5.6 g (56.2%) of 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide as Form R-5.

Workup

  1. customat 20-25° C.
  2. distillationfollowed by the distillation of 15 ml at 35-40° C. under vacuum, in order
  3. customto remove the remaining HCl
  4. temperatureThe reaction was cooled to 20-25° C.
  5. waitthe mixture was left
  6. stirringunder powerful stirring over 4 h at 20-25° C
  7. filtrationwas filtered
  8. washwashed twice with 50 ml of a saturated aqueous sodium bicarbonate solution and twice with 50 ml of water The solid
  9. customwas dried on a vacuum drier at 50° C.

Sources & evidence

ORD record
ord-c76100d850494e598273b8dfb09aaa8c
Source dataset
uspto-grants-2014_11
Patent number
US08884026B2

Reaction notes

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