Water → (3-(4-Fluorophenyl)-5-methylisoxazol-4-yl)methanol

HRID 1625918Notes

Reaction equation

HRID 1625918 reaction equation
C([O:3][C:4]([C:6]1[C:7]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[N:8][O:9][C:10]=1[CH3:11])=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[F:18][C:15]1[CH:14]=[CH:13][C:12]([C:7]2[C:6]([CH2:4][OH:3])=[C:10]([CH3:11])[O:9][N:8]=2)=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 22309061Ethyl 3-(4-fluorophenyl)-5-methyl-1,2-oxazole-4-carboxylate

Product 1

HCID 28473136(3-(4-Fluorophenyl)-5-methylisoxazol-4-yl)methanolYield 72.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(4-fluoro-phenyl)-5-methyl-isoxazole-4-carboxylic acid ethyl ester (3.0 g, 12 mmol) (6.18 g, 25 mmol) in THF (320 mL) was added portionwise lithiumaluminiumhydride (528 mg, 14 mmol) at 0° C. and the reaction mixture was stirred at room temperature for 3 h. The mixture was then cooled to 0° C. and water (518 μL) added followed by sodium hydroxide (15% solution, 518 μL) and then again water (1.5 mL) and the mixture then stirred overnight at room temperature. The precipitate was then filtered off and washed with THF. The combined washings and filtrate were then evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1) afforded the title compound (1.8 g, 71%) which was obtained as a white solid. MS: m/e=208.1 [M+H]+.

Workup

  1. temperatureThe mixture was then cooled to 0° C.
  2. filtrationThe precipitate was then filtered off
  3. washwashed with THF
  4. customThe combined washings and filtrate were then evaporated
  5. customPurification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1)

Sources & evidence

ORD record
ord-b6644c1e554a43feb922826221b7c8ef
Source dataset
uspto-grants-2014_07
Patent number
US08785435B2

Reaction notes

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