Sodium Chloride → 2-Methyl-6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridine

HRID 1520972Notes

Reaction equation

HRID 1520972 reaction equation
[H-].[Na+].[CH3:3][C:4]1[O:8][N:7]=[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:5]=1[CH2:15][OH:16].F[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:19]=1.[Cl-].[Na+]>C1COCC1>[CH3:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([O:16][CH2:15][C:5]2[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[N:7][O:8][C:4]=2[CH3:3])[N:19]=1

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 24758Sodium hydrideHCID 960902-Fluoro-6-methylpyridineHCID 2776149(5-Methyl-3-phenyl-1,2-oxazol-4-yl)methanol

Product 1

HCID 575198312-Methyl-6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridineYield 48.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (55% dispersion in mineral oil, 48 mg, 1.1 mmol) in THF (1.5 mL) was added a solution of (5-methyl-3-phenyl-isoxazol-4-yl)-methanol (189 mg, 1.0 mmol) in THF (3 mL) at 0° C. and the reaction mixture warmed to room temperature over 30 min. Then a solution of 2-fluoro-6-methylpyridine (122 mg, 1.1 mmol) in THF (3 mL) was added dropwise at 0° C. and the reaction mixture was stirred at room temperature overnight. The reaction mixture was then poured into aqueous sodium chloride (saturated) 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=100:0 to 4:1) afforded the title compound (135 mg, 48%) which was obtained as a yellow oil. MS: m/e=281.1 [M+H]+.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe combined organic layers were then washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customPurification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 4:1)

Sources & evidence

ORD record
ord-9c5ec5ad30ba4f57950196e7301f1997
Source dataset
uspto-grants-2015_07
Patent number
US09073908B2

Reaction notes

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