1H-1,2,4-Triazole → HCID 13254744, compound

HRID 1199880Notes

Reaction equation

HRID 1199880 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[Na].[F:7][C:8]1[CH:23]=[CH:22][C:11]([O:12][CH2:13][C:14]2([C:17]([CH3:21])([CH3:20])[CH2:18][F:19])[CH2:16][O:15]2)=[CH:10][CH:9]=1>C(O)CC>[F:19][CH2:18][C:17]([CH3:21])([CH3:20])[C:14]([CH2:13][O:12][C:11]1[CH:10]=[CH:9][C:8]([F:7])=[CH:23][CH:22]=1)([OH:15])[CH2:16][N:1]1[CH:5]=[N:4][CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 5360545SodiumHCID 13254739HCID 13254739, compound

Product 1

HCID 13254744HCID 13254744, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent2×

Procedure

15.2 g (0.22 mol) of 1,2,4-triazole were added to 0.46 g (0.02 mol) of sodium in 200 ml of n-propanol. The solution was heated to the boil, and 48.5 g (0.2 mol) of 2-(4-fluorophenoxymethyl)-2-(fluoro-tert.-butyl)-oxirane, dissolved in 50 ml of n-propanol, were added dropwise. The reaction solution was stirred under reflux for a further 48 hours and was concentrated, and 200 ml ethyl acetate and 100 ml of water were added to the residue. The organic phase was separated off, washed twice with water, dried over sodium sulphate and concentrated. The residue was dissolved in ether, and the solution was gassed with hydrogen chloride. The precipitate formed was filtered off under suction and washed with ether, and ethyl acetate/1N sodium hydroxide solution were added. The crude product obtained was purified over a silica gel column (mobile phase: methylene chloride/ethyl acetate, 2:1), and recrystallised from acetonitrile. 17.9 g (29% of theory) of 4-fluoro-2-(4-fluorophenoxymethyl)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)-butan-2-ol of melting point 97° to 99° C. were obtained.

Workup

  1. additionwere added dropwise
  2. temperatureunder reflux for a further 48 hours
  3. concentrationwas concentrated
  4. addition200 ml ethyl acetate and 100 ml of water were added to the residue
  5. customThe organic phase was separated off
  6. washwashed twice with water
  7. dry with materialdried over sodium sulphate
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in ether
  10. customThe precipitate formed
  11. filtrationwas filtered off under suction
  12. washwashed with ether, and ethyl acetate/1N sodium hydroxide solution
  13. additionwere added
  14. customThe crude product obtained
  15. customwas purified over a silica gel column (mobile phase: methylene chloride/ethyl acetate, 2:1)
  16. customrecrystallised from acetonitrile

Sources & evidence

ORD record
ord-6de9de8cc8454faf8360a9ecf401f7af
Source dataset
uspto-grants-1990_02
Patent number
US04904296

Reaction notes

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