Water → [3-(5-Fluoro-pyridin-2-yl)-isoxazol-4-yl]-methanol

HRID 83464Notes

Reaction equation

HRID 83464 reaction equation
C([O:3][C:4]([C:6]1[C:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)=[N:8][O:9][CH:10]=1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:7]2[C:6]([CH2:4][OH:3])=[CH:10][O:9][N:8]=2)=[N:12][CH:13]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 666436143-(5-Fluoro-pyridin-2-yl)-isoxazole-4-carboxylic acid ethyl ester

Product 1

HCID 66643813[3-(5-Fluoro-pyridin-2-yl)-isoxazol-4-yl]-methanolYield 30.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(5-fluoro-pyridin-2-yl)-isoxazole-4-carboxylic acid ethyl ester (1.0 g, 4.23 mmol) in THF (52 mL) was added portionwise lithiumaluminiumhydride (89 mg, 2.33 mmol) at 0° C. and the reaction mixture was stirred at room temperature for 1 h. The mixture was then cooled to 0° C. and water (88 μL) added followed by sodium hydroxide (15% solution, 88 μL) and then again water (264 μL) 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 (249 mg, 30%) which was obtained as a light yellow solid. MS: m/e=195.1 [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-fd798b737fdc4404b3181d283cfcdfc1
Source dataset
uspto-grants-2014_09
Patent number
US08846719B2

Reaction notes

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