Sodium hydride → 5-Bromo-2-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-pyridine

HRID 83234Notes

Reaction equation

HRID 83234 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][OH:14])=[C:11]([CH3:15])[O:10][N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:19]1[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][N:20]=1>C1COCC1.CO.O>[Br:25][C:22]1[CH:23]=[CH:24][C:19]([O:14][CH2:13][C:12]2[C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[N:9][O:10][C:11]=2[CH3:15])=[N:20][CH:21]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 27344145-Bromo-2-chloropyridineHCID 28473136(3-(4-Fluorophenyl)-5-methylisoxazol-4-yl)methanol

Product 1

HCID 684428165-Bromo-2-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-pyridineYield 15%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a a solution of [3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-methanol (500 mg, 2.41 mmol) in THF (5 mL) at room temperature was added sodium hydride (55% dispersion in mineral oil, 137 mg, 3.1 mmol) and the reaction mixture stirred at room temperature for 1 h. Then a solution of 2-chloro-5-bromo-pyridine (484 mg, 2.41 mmol) in THF (5 mL) was added at room temperature and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was then diluted with methanol and water and the mixture was extracted with ethyl acetate. The combined organic layers were then washed with water and brine and then dried over sodium sulfate, filtered and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=9:1 to 4:1) afforded the title compound (128 mg, 15%) which was obtained as a colourless oil. MS: m/e=363.1/365.1 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 2 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined organic layers were then washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by chromatography (SiO2, heptane:ethyl acetate=9:1 to 4:1)

Sources & evidence

ORD record
ord-7e397fdfbd7a4d66bded24d43b2f4cde
Source dataset
uspto-grants-2014_09
Patent number
US08846719B2

Reaction notes

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