5-(4-(1H-1,2,4-triazol-1-yl)benzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione → 2-(4-(1H-1,2,4-triazol-1-yl)benzyl)malonic acid

HRID 928792Notes

Reaction equation

HRID 928792 reaction equation
[N:1]1([C:6]2[CH:22]=[CH:21][C:9]([CH2:10][CH:11]3[C:16](=[O:17])[O:15]C(C)(C)[O:13][C:12]3=[O:20])=[CH:8][CH:7]=2)[CH:5]=[N:4][CH:3]=[N:2]1>O.FC(F)(F)C(O)=O>[N:1]1([C:6]2[CH:7]=[CH:8][C:9]([CH2:10][CH:11]([C:12]([OH:20])=[O:13])[C:16]([OH:17])=[O:15])=[CH:21][CH:22]=2)[CH:5]=[N:4][CH:3]=[N:2]1

Participants

4

Reactant 1

HCID 867156245-(4-(1H-1,2,4-triazol-1-yl)benzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione2×

Product 1

HCID 867156252-(4-(1H-1,2,4-triazol-1-yl)benzyl)malonic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
65 °C

Procedure

5-(4-(1H-1,2,4-triazol-1-yl)benzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (10.0 g, 33.2 mmol, Intermediate 45, step b) was dissolved in a mixture of water (30 mL) and trifluoroacetic acid (50 mL). The mixture was heated to 65° C. After 2.5 hours, the mixture was allowed to cool to 23° C. Water and trifluoroacetic acid were removed by rotary evaporation at 45° C. Toluene (100 mL) was added to the residue then the mixture was concentrated by rotary evaporation at 45° C. Tetrahydrofuran (100 mL) and 6 M aqueous hydrochloric acid solution (28 mL) was added to the residue in sequence. The resulting heterogeneous mixture was stirred at 23° C. After 10 minutes, the mixture was concentrated by rotary evaporation at 45° C. Tetrahydrofuran (100 mL) was added to the residue and the mixture concentrated by rotary evaporation at 45° C. Toluene (100 mL) was added to the residue and the mixture concentrated by rotary evaporation at 45° C. The resulting white solid was dried under vacuum at 40° C. The solid product was used directly in the next step without further purification.

Workup

  1. temperatureto cool to 23° C
  2. customWater and trifluoroacetic acid were removed by rotary evaporation at 45° C
  3. additionToluene (100 mL) was added to the residue
  4. concentrationthe mixture was concentrated by rotary evaporation at 45° C
  5. additionTetrahydrofuran (100 mL) and 6 M aqueous hydrochloric acid solution (28 mL) was added to the residue in sequence
  6. waitAfter 10 minutes
  7. concentrationthe mixture was concentrated by rotary evaporation at 45° C
  8. additionTetrahydrofuran (100 mL) was added to the residue
  9. concentrationthe mixture concentrated by rotary evaporation at 45° C
  10. additionToluene (100 mL) was added to the residue
  11. concentrationthe mixture concentrated by rotary evaporation at 45° C
  12. customThe resulting white solid was dried under vacuum at 40° C
  13. customThe solid product was used directly in the next step without further purification

Sources & evidence

ORD record
ord-4561d57fbf4c43ab9a44de6e5ea14962
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

Loading…