Hydrochloric Acid → 4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzoic acid

HRID 2207010Notes

Reaction equation

HRID 2207010 reaction equation
[F:1][C:2]([F:29])([O:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH:18]=[N:17][C:16]([C:19]3[CH:28]=[CH:27][C:22]([C:23]([O:25]C)=[O:24])=[CH:21][CH:20]=3)=[N:15]2)=[CH:10][CH:9]=1)[C:3]([F:6])([F:5])[F:4].C1COCC1.O.[OH-].[Li+].Cl>O>[F:29][C:2]([F:1])([O:7][C:8]1[CH:9]=[CH:10][C:11]([N:14]2[CH:18]=[N:17][C:16]([C:19]3[CH:20]=[CH:21][C:22]([C:23]([OH:25])=[O:24])=[CH:27][CH:28]=3)=[N:15]2)=[CH:12][CH:13]=1)[C:3]([F:6])([F:5])[F:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 90402708methyl 4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzoate

Product 1

HCID 782101774-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzoic acidYield 96%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
23 °C

Procedure

In a 250 mL round bottom flask equipped with an overhead stirrer, thermocouple, and nitrogen inlet was added methyl 4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzoate (11.1 g, 26.9 mmol) and THF (100 mL). To this yellow suspension was added water (10 mL) and lithium hydroxide monohydrate (3.4 g, 81 mmol). There was no change in reaction appearance and temperature (20.5° C.). The reaction was stirred at 23° C. for 39 h during which it became a yellow solution. A heating mantle was attached to the reaction flask and the flask was heated to an internal temperature of 60° C. for 2.5 hrs. The reaction was then cooled to 4° C. in an ice bath and water (100 mL) was added, providing a light yellow solution. Concentrated HCl (8.0 g) was added (note: exothermic) which gave a thick white precipitate. The white suspension was stirred at 5° C. for 30 min and then the solid was collected by vacuum filtration and washed with water (2×25 mL). The white wet cake was allowed to dry in air for 3 h, and was then placed into a vacuum oven (50° C., 700 mm Hg vacuum, 16 h). This gave the title compound as a white solid (10.3 g, 96%): mp 227-229° C.; 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 8.32 (d, J=8.4 Hz, 2H), 8.23 (d, J=8.4 Hz, 2H), 7.84 (d, J=8.9 Hz, 1H), 7.42 (d, J=8.9 Hz, 2H).

Workup

  1. customIn a 250 mL round bottom flask equipped with an overhead stirrer
  2. customin reaction appearance and temperature (20.5° C.)
  3. temperaturethe flask was heated to an internal temperature of 60° C. for 2.5 hrs
  4. temperatureThe reaction was then cooled to 4° C. in an ice bath
  5. customproviding a light yellow solution
  6. customgave a thick white precipitate
  7. stirringThe white suspension was stirred at 5° C. for 30 min
  8. filtrationthe solid was collected by vacuum filtration
  9. washwashed with water (2×25 mL)
  10. customto dry in air for 3 h
  11. customwas then placed into a vacuum oven (50° C., 700 mm Hg vacuum, 16 h)

Sources & evidence

ORD record
ord-6d43da9abe12430d9e1249c751fbbccd
Source dataset
uspto-grants-2016_06
Patent number
US09376401B2

Reaction notes

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