Dimethylformamide → Rufinamide

HRID 335514Notes

Reaction equation

HRID 335514 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.C[N:25](C=O)C>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

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 10014469Cgp-47292

Product 1

HCID 129228RufinamideYield 65.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

75.4 ml of Oxalyl chloride (919.8 mmol) were added at 25° C. to a stirred suspension of (2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (200.0 g, 836.2 mmol) in THF (500 ml) and DMF (0.5 ml). The stirring was maintained for 4 hr at 25° C. until the solid dissolved. Afterwards, 1000 ml of THF were added and reduced pressure (200-250 mbar) was applied leading to the distillation of 300 ml of THF and to the maintenance of the internal temperature at about 25-35° C. After that, the mixture was slightly cool to 25° C. and 160 g of ammonium chloride were added in portions followed by slow addition of 400 ml of an 8% NaHCO3 solution and 176 g of solid NaHCO3 (vigorous stirring was also needed to prevent frothing). The heterogeneous mixture was stirred for 2 hr, filtered and the solid re-suspended in 1 L water. The solid was filtered and dried (at 200 mbar/50° C.) yielding 130 g (65.3%) of 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide, as a white solid in form R5.

Workup

  1. dissolutiondissolved
  2. distillationreduced pressure (200-250 mbar) was applied leading to the distillation of 300 ml of THF and to the maintenance of the internal temperature at about 25-35° C
  3. temperatureAfter that, the mixture was slightly cool to 25° C.
  4. addition160 g of ammonium chloride were added in portions
  5. additionfollowed by slow addition of 400 ml of an 8% NaHCO3 solution and 176 g of solid NaHCO3 (
  6. stirringThe heterogeneous mixture was stirred for 2 hr
  7. filtrationfiltered
  8. filtrationThe solid was filtered
  9. customdried (at 200 mbar/50° C.)

Sources & evidence

ORD record
ord-52988d137bff468598ed43a360e0388a
Source dataset
uspto-grants-2014_11
Patent number
US08884026B2

Reaction notes

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