Lithium hydroxide, monohydrate → HCID 58374133, compound

HRID 1804507Notes

Reaction equation

HRID 1804507 reaction equation
[CH2:1]([C:5]1[O:9][N:8]=[C:7]([C:10]([O:12]C)=[O:11])[C:6]=1[C:14]([F:17])([F:16])[F:15])[CH:2]([CH3:4])[CH3:3].O.[OH-].[Li+]>CO.O>[CH2:1]([C:5]1[O:9][N:8]=[C:7]([C:10]([OH:12])=[O:11])[C:6]=1[C:14]([F:17])([F:16])[F:15])[CH:2]([CH3:4])[CH3:3]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 58374113HCID 58374113, compound

Product 1

HCID 58374133HCID 58374133, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of methyl 5-isobutyl-4-(trifluoromethyl)isoxazole-3-carboxylate (0.816 g, 3.25 mmol) and lithium hydroxide hydrate (0.136 g, 3.25 mmol) in methanol (18 mL) and water (9.00 mL) was stirred at room temperature overnight. HPLC and LCMS analysis indicated that the hydrolysis was complete. The reaction mixture was concentrated under reduced pressure, and the residue dissolved in 1N aqueous hydrochloric acid and extracted with ether. The organic layer was collected and dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded 5-isobutyl-4-(trifluoromethyl)isoxazole-3-carboxylic acid (0.746 g, 3.15 mmol, 97% yield) as an off-white solid. The product had an HPLC ret. time=2.00 min.−Column. CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.91 (s, 3H), 0.93 (s, 3H), 1.97-2.09 (m, 1H), and 2.89 (d, J=7.28 Hz, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue dissolved in 1N aqueous hydrochloric acid
  3. extractionextracted with ether
  4. customThe organic layer was collected
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-4a0096e0eea148b1aeba52565ff6f1d0
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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