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

HRID 514746Notes

Reaction equation

HRID 514746 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.[OH-].[Li+]>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

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 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
60 °C

Procedure

In a 250 mL round bottomed flask equipped with an overhead stirrer, T-type thermocouple, and nitrogen inlet were 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 were added water (10 mL) and lithium hydroxide.monohydrate (LiOH.H2O; 3.4 g, 81 mmol). The reaction was stirred at 23° Cfor 39 h during which time it became a yellow solution. The solution was warmed to 60° C. and stirred at 60° C. until complete by LC-MS. The reaction was cooled to 4° C. in an icebath and water (100 mL) was added to give a light yellow solution. Concentrated HCI (8.0 g) was added (note: exothermic) resulting in a thick white precipitate. The white suspension was stirred at 5° C. for 30 min and then the solid was collected by vacuum filtration. The filter cake was washed with water (2×25 mL), air dried for 3 h, and dried under vacuum (700 mm Hg) at 50° C. for 16 h to give the title compound as a white solid (10.3 g, 96%): mp 227-229° C.; 1H NMR (400 MHz, CDCI3) 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 bottomed flask equipped with an overhead stirrer
  2. stirringstirred at 60° C. until complete by LC-MS
  3. additionwas added
  4. customto give a light yellow solution
  5. additionConcentrated HCI (8.0 g) was added (note: exothermic)
  6. customresulting in 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. washThe filter cake was washed with water (2×25 mL), air
  10. customdried for 3 h
  11. customdried under vacuum (700 mm Hg) at 50° C. for 16 h

Sources & evidence

ORD record
ord-26e9ce6e77e9409e960084b95c1a5238
Source dataset
uspto-grants-2015_08
Patent number
US09108932B2

Reaction notes

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