Lithium hydroxide, monohydrate → 2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)acetic acid

HRID 573811

Reaction equation

HRID 573811 reaction equation
[F:1][C:2]([F:27])([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([O:24]C)=[O:23])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.O.[OH-].[Li+]>O1CCCC1.CO.O>[F:27][C:2]([F:1])([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([OH:24])=[O:23])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 90405381methyl 2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)acetate

Product 1

HCID 904042172-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)acetic acidYield 98.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 100 mL round bottomed flask, equipped with a magnetic stir bar, was added methyl 2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)acetate (C3) (3.45 g, 9.14 mmol) and lithium hydroxide-hydrate (1.15 g, 27.4 mmol) as solids. These solids were diluted with tetrahydrofuran (24 mL), methanol (24 mL), and water (12 mL). The reaction was stirred at room temperature for 2 hours. The reaction mixture was then concentrated to dryness. The resulting solid was then diluted with water, and the resulting suspension was adjusted to pH 2.9. The subsequent precipitate was extracted with ethyl acetate (5×100 mL). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated to afford the title compound as a white solid (3.27 g, 96%): 1H NMR (400 MHz, DMSO-d6) δ 12.41 (s, 1H), 9.40 (s, 1H), 8.15-8.03 (m, 4H), 7.63 (dq, J=7.9, 1.0 Hz, 2H), 7.49-7.36 (m, 2H), 3.66 (s, 2H); 19F NMR (376 MHz, DMSO-d6) δ −56.98; ESIMS m/z 364 ([M+H]+).

Workup

  1. customTo a 100 mL round bottomed flask, equipped with a magnetic stir bar
  2. concentrationThe reaction mixture was then concentrated to dryness
  3. additionThe resulting solid was then diluted with water
  4. extractionThe subsequent precipitate was extracted with ethyl acetate (5×100 mL)
  5. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-2360d1173a1e445491b3e8f28d8d5980
Source dataset
uspto-grants-2015_05
Patent number
US09029560B2

Linked notes

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