Hydrochloric Acid → (2E)-3-[4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]acrylic acid

HRID 30633

Reaction equation

HRID 30633 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[N:11][N:10]=[C:9]2[CH:13]=O)=[CH:4][CH:3]=1.C(OP([CH2:23][C:24]([O:26]CC)=[O:25])(OCC)=O)C.[H-].[Na+].Cl>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:12]=[N:11][N:10]=[C:9]2/[CH:13]=[CH:23]/[C:24]([OH:26])=[O:25])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 838776134-(4-fluorophenyl)-4H-1,2,4-triazole-3-carbaldehyde

Product 1

HCID 69209208(2E)-3-[4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]acrylic acidYield 77.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-(4-fluorophenyl)-4H-1,2,4-triazole-3-carbaldehyde (3.83 g), ethyl diethylphosphonoacetate (5.60 g), sodium hydride (60% in oil, 0.88 g) and tetrahydrofuran (130 ml) was stirred at 0° C. for 1 hr. The reaction mixture was poured into an aqueous dilute hydrochloric acid solution and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was dissolved in a 6N aqueous hydrochloric acid solution (100 ml) and stirred for 2 hrs. with heating under reflux. Disodium hydrogen phosphate was added to neutralize the reaction mixture. The precipitated solids were collected by filtration, washed with water and dried to give (2E)-3-[4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]acrylic acid (3.60 g, yield 76%) as pale-yellow crystals. melting point: 226-229° C. (recrystallized from ethyl acetate-hexane).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in a 6N aqueous hydrochloric acid solution (100 ml)
  6. stirringstirred for 2 hrs
  7. temperaturewith heating
  8. temperatureunder reflux
  9. additionDisodium hydrogen phosphate was added
  10. filtrationThe precipitated solids were collected by filtration
  11. washwashed with water
  12. customdried

Sources & evidence

ORD record
ord-f587e4f7f1cf4ddc8ddbbf4804b567ee
Source dataset
uspto-grants-2008_09
Patent number
US07423159B2

Linked notes

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