Lithium hydroxide, monohydrate → HCID 58374151, compound

HRID 77117Notes

Reaction equation

HRID 77117 reaction equation
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]([O:14]CC)=[O:13])[C:8]=2[C:17]([F:20])([F:19])[F:18])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.[OH-].[Li+]>CO.O>[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]([OH:14])=[O:13])[C:8]=2[C:17]([F:19])([F:20])[F:18])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66955079Ethyl 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylate

Product 1

HCID 58374151HCID 58374151, compoundYield 96.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of ethyl 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylate (3.6 g, 12.6 mmol) in methanol (100 mL) and water (20 mL) at room temperature was added lithium hydroxide, monohydrate (0.583 g, 13.9 mmol). The reaction mixture was stirred at room temperature for 30 minutes. The methanol was removed under reduce pressure, and the residue was diluted with water (˜100 mL). Ethyl ether (200 mL) was added, and the pH of the aqueous layer was adjusted to <1 with a 1N aqueous solution of hydrochloric acid. The mixture was transferred to a separatory funnel, and after agitation, the layers were separated. The organic layer was washed with brine (100 mL), dried over anhydrous magnesium sulfate, and concentrated to afford 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylic acid (3.12 g, 12.13 mmol, 96% yield) as a white, crystalline solid. The compound had an HPLC retention time=2.58 minutes (YMC-Combi 4.6×50 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.2% phosphoric acid over a 4 minute gradient. MS:(M+Na)=279.95. 1H NMR (400 MHz, CDCl3) δ ppm 7.53-7.64 (m, 3H), and 7.70 (d, J=7.5 Hz, 2H).

Workup

  1. customThe methanol was removed
  2. additionthe residue was diluted with water (˜100 mL)
  3. additionEthyl ether (200 mL) was added
  4. customThe mixture was transferred to a separatory funnel
  5. customafter agitation, the layers were separated
  6. washThe organic layer was washed with brine (100 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-0ee2e35ba6804c18b15d1428fcc94553
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

Loading…