Lithium hydroxide, monohydrate → 4-[6-(Trifluoromethyl)pyridin-3-yl]benzoic acid

HRID 1677131Notes

Reaction equation

HRID 1677131 reaction equation
C[O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:14][CH:15]=2)=[CH:6][CH:5]=1.O.[OH-].[Li+]>O1CCCC1.O>[F:18][C:16]([F:17])([F:19])[C:13]1[N:12]=[CH:11][C:10]([C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:20])=[O:2])=[CH:5][CH:6]=2)=[CH:15][CH:14]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 67370143HCID 67370143, compound

Product 1

HCID 231205374-[6-(Trifluoromethyl)pyridin-3-yl]benzoic acid

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

Procedure F′: 5-Bromo-2-trifluoromethylpyridine (Eur J. Org Chem (2003), 1559) (0.85 g, 3.7 mmol), methoxycarbonylphenyl-4-boronic acid (0.44 g, 2.4 mmol) and sodium carbonate (1 g, 9.4 mmol) are suspended in dioxane/water (9:1) (25 ml). The mixture is degassed for 20 minutes with a nitrogen stream, tetrakis(triphenylphosphine) palladium (0.05 g, 0.04 mmol) is added and the mixture is heated to reflux under nitrogen overnight. The mixture is concentrated under reduced pressure and partitioned between water and ethyl acetate. The aqueous layer is extracted several times with ethyl acetate. The combined organic layers are dried over MgSO4 and evaporated. The crude product is purified by silica-gel column chromatography (gradient 10% ethyl acetate in cyclohexane to 10% cyclohexane in ethyl acetate) to give 4-(6-trifluoromethyl-pyridin-3-yl)-benzoic acid methyl ester. MS (FIA) 282.0 (MH+). Procedure G′: 4-(6-Trifluoromethyl-pyridin-3-yl)-benzoic acid methyl ester (0.57 g, 2 mmol) is dissolved in tetrahydrofuran/water (9:1) (25 ml), lithium hydroxide monohydrate (0.9 g, 2.2 mmol) is added and the mixture is heated under reflux overnight. The mixture is concentrated under reduced pressure and partitioned between water and ethyl acetate. The aqueous layer is acidified and the resulting precipitate is collected by filtration to give the 4-(6-trifluoromethyl-pyridin-3-yl)-benzoic acid. MS (FIA) 267 (MH−)

Workup

  1. temperaturethe mixture is heated
  2. temperatureunder reflux overnight
  3. concentrationThe mixture is concentrated under reduced pressure
  4. custompartitioned between water and ethyl acetate
  5. filtrationthe resulting precipitate is collected by filtration

Sources & evidence

ORD record
ord-c58d6db523ef4e2989a959004dfb3242
Source dataset
uspto-grants-2011_08
Patent number
US08008301B2

Reaction notes

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