Lithium hydroxide, monohydrate → HCID 58374133, compound

HRID 1948463Notes

Reaction equation

HRID 1948463 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. By HPLC and LCMS, 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-7678b0daca3e468a84953f218c82e690
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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