Ammonium Chloride → Rufinamide

HRID 335512Notes

Reaction equation

HRID 335512 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.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]([NH2:25])=[O:17])[N:13]=[N:12]1

Participants

7

Reactant 4

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

Product 1

HCID 129228RufinamideYield 55.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
22.5 °C

Procedure

1.9 ml (22.4 mmol) of oxalyl chloride were added drop wise, to a suspension of 5 g (20.9 mmol) of 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid in 12.5 ml of anhydrous THF, at 20-25° C. and under nitrogen atmosphere. Once the addition of oxalyl chloride was completed, the mixture was stirred at 20-25° C. for 4 h. Afterwards, the resulting mixture was concentrated under vacuum to dryness, in order to eliminate HCl and unreacted oxalyl chloride. The obtained residue was dissolved in ml of fresh anhydrous THF and treated with 4.0 g (75.2 mmol) of ammonium chloride and 5.26 g (62.7 mmol) of sodium bicarbonate over 16 h at 20-25° C. The resultant suspension was treated with 30 ml of water. The solid was filtrated and washed with 30 ml of a saturated aqueous sodium bicarbonate solution and twice with 30 ml of water. The solid was dried in a vacuum drier at 50° C. to yield 2.78 g (55.8%) of 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide as Form R-5.

Workup

  1. customat 20-25° C.
  2. concentrationAfterwards, the resulting mixture was concentrated under vacuum to dryness, in order
  3. filtrationThe solid was filtrated
  4. washwashed with 30 ml of a saturated aqueous sodium bicarbonate solution and twice with 30 ml of water
  5. customThe solid was dried in a vacuum drier at 50° C.

Sources & evidence

ORD record
ord-9045e347ccd5412a82438a066d2884db
Source dataset
uspto-grants-2014_11
Patent number
US08884026B2

Reaction notes

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