Ammonium Hydroxide → Riluzole

HRID 2422463Notes

Reaction equation

HRID 2422463 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. 1H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J=2.2 Hz, 1H), 7.63 (s, 2H), 7.36 (d, J=8.7 Hz, 1H), 7.17 (dd, J=8.7, 2.4 Hz, 1H), 3.23 (s, 3H). MS (EI): m/z 235 (M+H).

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-a76e86e4cc074ba1bbea95d93cf8d342
Source dataset
uspto-grants-2011_06
Patent number
US07960408B2

Reaction notes

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