Hydrogen Bromide → Falnidamol

HRID 1840635Notes

Reaction equation

HRID 1840635 reaction equation
[OH-].[Na+].Cl[C:4]1[N:5]=[C:6]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[C:28]([Cl:33])[CH:27]=2)[C:7]2[N:8]=[C:9]([NH:17][CH:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[N:10](C(=O)C)[CH2:11][C:12]=2[N:13]=1.Br.OO>O.[Pd].C(O)=O.C1COCC1.CO>[Cl:33][C:28]1[CH:27]=[C:26]([NH:25][C:6]2[C:7]3[N:8]=[C:9]([NH:17][CH:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[N:10]=[CH:11][C:12]=3[N:13]=[CH:4][N:5]=2)[CH:31]=[CH:30][C:29]=1[F:32]

Participants

10

Reactant 4

HCID 260Hydrogen BromideHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 178473742HCID 178473742, compound

Product 1

HCID 6918508Falnidamol

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 284Formic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

9 ml of 2N sodium hydroxide solution are added to a mixture of 9 g (0.019 mol) of (4), 81 ml of methanol and 9 ml of THF and the mixture is refluxed for 1 hour. Then 0.45 g of Pd/C (10%) are added and 4.5 ml of formic acid are added dropwise at boiling temperature. The mixture is refluxed for 24 hours, filtered off and evaporated down in vacuo to leave a residue. This is taken up in 90 ml of water and 7.2 ml of conc. hydrobromic acid and combined at ambient temperature with 3.9 ml of hydrogen peroxide (30%). The mixture is stirred for 5 hours at ambient temperature, then the product that crystallises out is filtered off and washed with water. The filter residue is dissolved in methanol, the free base is precipitated by the addition of 30 ml of water and 2N sodium hydroxide solution. Yield: 4.95 g (66%)

Workup

  1. temperaturethe mixture is refluxed for 1 hour
  2. temperatureThe mixture is refluxed for 24 hours
  3. filtrationfiltered off
  4. customevaporated down in vacuo
  5. customto leave a residue
  6. customthe product that crystallises out
  7. filtrationis filtered off
  8. washwashed with water
  9. dissolutionThe filter residue is dissolved in methanol
  10. customthe free base is precipitated by the addition of 30 ml of water and 2N sodium hydroxide solution

Sources & evidence

ORD record
ord-6abfe298393c46afae0bae4ae82443d5
Source dataset
uspto-grants-2004_01
Patent number
US06680384B2

Reaction notes

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