Water → (3-(2-Fluorophenyl)-5-methylisoxazol-4-yl)methanol

HRID 1521052Notes

Reaction equation

HRID 1521052 reaction equation
C([O:3][C:4]([C:6]1[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[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:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:7]1[C:6]([CH2:4][OH:3])=[C:10]([CH3:11])[O:9][N:8]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 68442729Ethyl 3-(2-fluorophenyl)-5-methylisoxazole-4-carboxylate

Product 1

HCID 68444673(3-(2-Fluorophenyl)-5-methylisoxazol-4-yl)methanolYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-(2-fluoro-phenyl)-5-methyl-isoxazole-4-carboxylic acid ethyl ester (73.6 g, 295 mmol) in THF (977 mL) was added portionwise lithiumaluminiumhydride (6.48 g, 162 mmol) over 20 min, at 0° C., and the reaction mixture was stirred at room temperature for 2.5 h. The mixture was then cooled to 0° C. and water (7.5 mL) added followed by sodium hydroxide (15% solution, 7.5 mL) and then again with water (21 mL). 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=75:25) afforded the title compound (34.7 g, 57%) which was obtained as a light yellow oil. MS: m/e=208.0 [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=75:25)

Sources & evidence

ORD record
ord-15420c59ddfc4b18915893045e4e7590
Source dataset
uspto-grants-2015_07
Patent number
US09073908B2

Reaction notes

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