Sodium hydride → 7-[1-(2,4-Difluorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine

HRID 1290810Notes

Reaction equation

HRID 1290810 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[OH:9].[H-].[Na+].Br[CH:13]([C:15]1[N:20]2[N:21]=[CH:22][N:23]=[C:19]2[N:18]=[CH:17][CH:16]=1)[CH3:14]>COCCOC>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[O:9][CH:13]([C:15]1[N:20]2[N:21]=[CH:22][N:23]=[C:19]2[N:18]=[CH:17][CH:16]=1)[CH3:14]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1230512,4-DifluorophenolHCID 189193517-(1-Bromoethyl)-1,2,4-triazolo[1,5-a]pyrimidine

Product 1

HCID 38018127-[1-(2,4-Difluorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent3×

Procedure

A solution of 2,4-difluorophenol (1.30 g) in dry 1,2-dimethoxyethane was added slowly to a stirred suspension of sodium hydride (0.48 g) in dry 1,2-dimethoxyethane (35 ml). The mixture was stirred for 30 minutes, then a solution of 7-(1-bromoethyl)-1,2,4-triazolo[1,5-a]pyrimidine (2.27 g, prepared in a similar manner to that described in Example 6) in dry 1,2-dimethoxyethane (85 ml) was added dropwise. The reaction mixture was stirred overnight at room temperature. The sodium bromide was removed from the mixture by filtration. The solvent was evaporated from the mixture and the residue was dissolved in dichloromethane and washed with 200 ml of a 5% aqueous solution of sodium hydroxide followed by water. Evaporation of the solvent afforded a crude product which was purified by column chromatography on silica gel using as eluent a mixture of dichloromethane and ethanol (in the ratio 97:3 respectively), followed by recrystallisation from a mixture of ethyl acetate and hexane, to give 7-[1-(2,4-difluorophenoxy)ethyl]-1,2,4-triazolo[1,5-a]pyrimidine. Yield 1.8 g, (m.p. 96°-97° C.).

Workup

  1. additionwas added dropwise
  2. stirringThe reaction mixture was stirred overnight at room temperature
  3. customThe sodium bromide was removed from the mixture by filtration
  4. customThe solvent was evaporated from the mixture
  5. dissolutionthe residue was dissolved in dichloromethane
  6. washwashed with 200 ml of a 5% aqueous solution of sodium hydroxide
  7. customEvaporation of the solvent
  8. customafforded a crude product which
  9. customwas purified by column chromatography on silica gel using as eluent
  10. additiona mixture of dichloromethane and ethanol (in the ratio 97:3 respectively),
  11. customfollowed by recrystallisation from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-e1f5453e550b48d9a4fbb290cf572457
Source dataset
uspto-grants-1998_05
Patent number
US05753665

Reaction notes

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