Hydrochloric Acid → Methyl [3-bromo-4-(3-fluorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-acetate

HRID 660881Notes

Reaction equation

HRID 660881 reaction equation
[Br:1][C:2]1[N:3]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[CH:10]=2)[C:4](=[O:7])[NH:5][N:6]=1.Cl[CH2:17][C:18]([O:20][CH3:21])=[O:19].C(=O)([O-])[O-].[K+].[K+].Cl>C(#N)C.C(OCC)(=O)C>[CH3:21][O:20][C:18](=[O:19])[CH2:17][N:5]1[C:4](=[O:7])[N:3]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[CH:10]=2)[C:2]([Br:1])=[N:6]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7295Methyl chloroacetateHCID 11430Potassium CarbonateHCID 580120875-bromo-4-(3-fluorobenzyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 58011964Methyl [3-bromo-4-(3-fluorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-acetate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

1.50 g (4.69 mmol) of the compound from Example 137A are stirred under reflux for 4 hrs together with 508 mg (4.69 mmol) of methyl chloroacetate and 1.30 g (9.4 mmol) of potassium carbonate in 33 ml acetonitrile. After cooling, the mixture is neutralized with 1 N hydrochloric acid and diluted with ethyl acetate. The organic phase is separated, washed with saturated sodium chloride solution, dried over sodium sulphate and freed of the volatile components on the rotary evaporator. The residue is dissolved in 20 ml dichloromethane and absorbed onto 3 g of diatomaceous earth. After removal of the solvent on the rotary evaporator the solid is transferred to a silica gel chromatography column and the product purified by elution with cyclohexane/ethyl acetate (gradient 5:1→1:1). 1.36 g (84% of theory) of the title compound are obtained.

Workup

  1. temperatureAfter cooling
  2. customThe organic phase is separated
  3. washwashed with saturated sodium chloride solution
  4. dry with materialdried over sodium sulphate
  5. customfreed of the volatile components on the rotary evaporator
  6. dissolutionThe residue is dissolved in 20 ml dichloromethane
  7. customabsorbed onto 3 g of diatomaceous earth
  8. customAfter removal of the solvent
  9. customon the rotary evaporator the solid
  10. customthe product purified by elution with cyclohexane/ethyl acetate (gradient 5:1→1:1)

Sources & evidence

ORD record
ord-359534aefba2463dbc1dfb4060510bda
Source dataset
uspto-grants-2011_12
Patent number
US08084481B2

Reaction notes

Loading…