Ammonium Hydroxide → Riluzole

HRID 1370516Notes

Reaction equation

HRID 1370516 reaction equation
[F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[CH:6][CH:5]=1.[C:13]([S-:15])#[N:14].[K+].BrBr.[NH4+].[OH-]>CC(O)=O>[F:1][C:2]([F:11])([F:12])[O:3][C:4]1[CH:10]=[CH:9][C:7]2[N:8]=[C:13]([NH2:14])[S:15][C:6]=2[CH:5]=1

Participants

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 24408BromineHCID 516872Potassium thiocyanateHCID 6008484-(Trifluoromethoxy)aniline

Product 1

HCID 5070RiluzoleYield 85.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

To a solution of 4-trifluoromethoxyaniline (Aldrich, 4.83 g, 30 mmol) in 50 mL of AcOH, was added KSCN (Aldrich, 11.64 g, 120 mmol). After the mixture was stirred for 30 min, a solution of bromine (Aldrich, 1.55 mL, 30 mmol) in 20 mL of AcOH was added over 30 min period, and the resulting reaction mixture was stirred overnight. The mixture was diluted with ice/water, brought to pH 8 with conc. NH4OH. The mixture extracted 3× with EtOAc (300 mL). The organic layers were washed twice with a brine solution (300 mL), dried over Na2SO4 and concentrated. The residue was purified by chromatography (40%-45% EtOAc/Hexanes) to give 6.0 g (85%) of product.

Workup

  1. customthe resulting reaction mixture
  2. stirringwas stirred overnight
  3. extractionThe mixture extracted 3× with EtOAc (300 mL)
  4. washThe organic layers were washed twice with a brine solution (300 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (40%-45% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-a9cda0f41afc4344bcf1ca0f5fff8ab2
Source dataset
uspto-grants-2003_06
Patent number
US06583157B2

Reaction notes

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