Water → 4-(5-bromo-2-fluorobenzyl)-5-methoxy-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 2296994Notes

Reaction equation

HRID 2296994 reaction equation
[CH3:1][O:2][C:3]1[NH:4][C:5](=[O:8])[NH:6][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[Br:15][C:16]1[CH:17]=[CH:18][C:19]([F:24])=[C:20]([CH:23]=1)[CH2:21]Br.O>C(#N)C>[Br:15][C:16]1[CH:17]=[CH:18][C:19]([F:24])=[C:20]([CH:23]=1)[CH2:21][N:4]1[C:3]([O:2][CH3:1])=[N:7][NH:6][C:5]1=[O:8]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium Carbonate2×HCID 135532954-Bromo-2-(bromomethyl)-1-fluorobenzeneHCID 1354997413H-1,2,4-Triazol-3-one, 1,2-dihydro-5-methoxy-2×

Product 1

HCID 183888114-(5-bromo-2-fluorobenzyl)-5-methoxy-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 24.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
55 °C

Procedure

To a solution of 5.75 g (50 mmol) of 5-methoxy-2,4-dihydro-3H-1,2,4-triazol-3-one in 30 ml of acetonitrile was added 6.21 g (45 mmol) of potassium carbonate. A solution of 13.54 g of crude 5-bromo-2-fluorobenzylbromide in 50 ml of acetonitrile was added dropwise at 55° C. thereto. After the mixture was stirred at 55° C. for 2.5 hours, 1.15 g of 5-methoxy-2,4-dihydro-3H-1,2,4-triazol-3-one and 1.24 g of potassium carbonate were added thereto and then the mixture was stirred at 55° C. for 3 hours. Water was added to the reaction mixture and the mixture was extracted with a mixed solvent of ethyl acetate and tert-butyl methyl ether. The organic layer was washed with water, dried and concentrated. Then, to the semisolid residue (13.37 g) was added a mixture of equal amounts of tert-butyl methyl ether and hexane, then stirred for a while and cooled. The resultant solid was collected by filtration to obtain 3.64 g of 4-(5-bromo-2-fluorobenzyl)-5-methoxy-2,4-dihydro-3H-1,2,4-triazol-3-one as white powder.

Workup

  1. stirringthe mixture was stirred at 55° C. for 3 hours
  2. extractionthe mixture was extracted with a mixed solvent of ethyl acetate and tert-butyl methyl ether
  3. washThe organic layer was washed with water
  4. customdried
  5. concentrationconcentrated
  6. additionThen, to the semisolid residue (13.37 g) was added
  7. additiona mixture of equal amounts of tert-butyl methyl ether and hexane
  8. stirringstirred for a while
  9. temperaturecooled
  10. filtrationThe resultant solid was collected by filtration

Sources & evidence

ORD record
ord-5b571dfc3dfb420b9a4092414598244f
Source dataset
uspto-grants-2002_12
Patent number
US06489487B1

Reaction notes

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