5-(trifluoromethyl)-4H-1,2,4-triazol-3-amine → N-(1,4-dioxaspiro[4.5]dec-8-yl)-5-(trifluoromethyl)-1H-1,2,4-triazol-3-amine

HRID 1688743Notes

Reaction equation

HRID 1688743 reaction equation
[F:1][C:2]([F:10])([F:9])[C:3]1[NH:7][N:6]=[C:5]([NH2:8])[N:4]=1.[O:11]1[C:15]2([CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]2)[O:14][CH2:13][CH2:12]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[O:11]1[C:15]2([CH2:20][CH2:19][CH:18]([NH:8][C:5]3[N:4]=[C:3]([C:2]([F:10])([F:9])[F:1])[NH:7][N:6]=3)[CH2:17][CH2:16]2)[O:14][CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 3508265-(trifluoromethyl)-4H-1,2,4-triazol-3-amineHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 67008537N-(1,4-dioxaspiro[4.5]dec-8-yl)-5-(trifluoromethyl)-1H-1,2,4-triazol-3-amineYield 42.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 5-(trifluoromethyl)-1H-1,2,4-triazol-3-amine (12.19 g) and 1,4-dioxaspiro[4.5]decan-8-one (12.49 g) in acetic acid (180 mL) was added sodium triacetoxyborohydride (25.43 g), and the mixture was stirred at room temperature for 3 days. The solvent was evaporated under reduced pressure, the residue was diluted with saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate-isopropyl alcohol (3:1). The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography [eluent: methanol/ethyl acetate=0/100→10/90 (volume ratio)] and crystallized from diisopropyl ether to give the title compound as a colorless solid (9.88 g, 42%).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. additionthe residue was diluted with saturated aqueous sodium hydrogen carbonate solution
  3. extractionthe mixture was extracted with ethyl acetate-isopropyl alcohol (3:1)
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel chromatography [eluent: methanol/ethyl acetate=0/100→10/90 (volume ratio)]
  8. customcrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-22d19bc57c454c72bf0a51bf49a4d16f
Source dataset
uspto-grants-2012_04
Patent number
US08148383B2

Reaction notes

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