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

HRID 1290813

Reaction equation

HRID 1290813 reaction equation
[Cl: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>[Cl: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 748142-Chloro-4-fluorophenolHCID 189193517-(1-Bromoethyl)-1,2,4-triazolo[1,5-a]pyrimidine

Product 1

HCID 98608677-[1-(2-Chloro-4-fluorophenoxy)ethyl]-1,2,4-triazolo[1,5-a]pyrimidine

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

A mixture of 2-chloro-4-fluorophenol (0.65 g) and sodium hydride (210 mg) in dry 1,2-dimethoxyethane (15 ml) was stirred at room temperature for 30 minutes. A solution of 7-(1-bromoethyl)-1,2,4-triazolo[1,5-a]pyrimidine (1 g, prepared in a similar manner to that described in Example 6) in 1,2-dimethoxyethane (35 ml) was added dropwise to the stirred mixture. The mixture was stirred at room temperature for 21 hours, then was filtered and the solvent was evaporated from the filtrate under reduced pressure. The residue was dissolved in dichloromethane, washed with a 5% aqueous solution of sodium hydroxide followed by water, dried over anhydrous magnesium sulphate and the solvent was evaporated under reduced pressure. The solid residue was purified by flash chromatography on silica gel using as eluent a mixture of ethyl acetate and petroleum ether (in the ratio 1:1), followed by recrystallisation from a mixture of ethyl acetate and hexane, to give 7-[1-(2-chloro-4-fluorophenoxy)ethyl]-1,2,4-triazolo[1,5-a]pyrimidine. Yield 0.99 g, (m.p. 89°-91° C.).

Workup

  1. additionwas added dropwise to the stirred mixture
  2. stirringThe mixture was stirred at room temperature for 21 hours
  3. filtrationwas filtered
  4. customthe solvent was evaporated from the filtrate under reduced pressure
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washwashed with a 5% aqueous solution of sodium hydroxide
  7. dry with materialdried over anhydrous magnesium sulphate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe solid residue was purified by flash chromatography on silica gel using as eluent
  10. additiona mixture of ethyl acetate and petroleum ether (in the ratio 1:1),
  11. customfollowed by recrystallisation from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-7e77ba517d1b4f09a392f3971d5bc6c4
Source dataset
uspto-grants-1998_05
Patent number
US05753665

Linked notes

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